AiPD: Autoinhibited Protein Database

Q01970

Gene name	PLCB3
Protein name	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3
Names	Phosphoinositide phospholipase C-beta-3, Phospholipase C-beta-3, PLC-beta-3
Species	Homo sapiens (Human)
KEGG Pathway	hsa:5331
EC number	3.1.4.11: Phosphoric diester hydrolases
Protein Class	PHOSPHOINOSITIDE-SPECIFIC PHOSPHOLIPASE C FAMILY PROTEIN (PTHR10336)

Descriptions

Phospholipase C-β proteins form a highly conserved enzyme family that hydrolyzes phosphatidylinositol 4,5-bisphosphate (PIP2) into the second messengers inositol 1,4,5-triphosphate (IP3) and diacylglycerol, which mobilize intracellular calcium and stimulate the activity of protein kinase C. PLCβ isoforms are activated through direct interactions with heterotrimeric G proteins of the Gαq family, Gβγ heterodimers and small GTPases such as Rac1. PLCβ proteins have a highly conserved catalytic core comprised of an N-terminal pleckstrin homology (PH) domain, followed by four EF hand domains, a triose phosphate isomerase (TIM) barrel-like catalytic domain split into X and Y halves by a variable linker (XY-linker), and a C2 domain. In the basal state, the Hα2’ helix packs against a highly conserved, hydrophobic cleft formed between the TIM barrel and C2 domain of the catalytic core, in close proximity to the active site and X-Y linker. Since the intermolecular interaction of the Hα1-Hα2 module with Gαq and the intramolecular interaction of Hα2′ with the catalytic core of PLCβ3 are competitive, disruption of the Hα2′-catalytic core interface enhances the affinity of Gαq for PLCβ3. In addition, deletion of the XY-linker enhances basal activity of the enzyme. Upon activation, Gαq-GTP directly binds the helix-turn-helix of PLCβ and reorients it away from membranes to relieve this component of steric occlusion of the lipase. Gαq simultaneously positions the catalytic core of PLCβ at the membrane interface, leading to repulsion of the XY-linker and opening the active site for catalysis. Activators of PLCβ isozymes use the membrane as a conduit to allosterically enhance the phospholipase activity of these enzymes.

Autoinhibitory domains (AIDs)

Target domain	318-468 (PI-PLC X domain); 590-706 (PI-PLC Y domain)
Relief mechanism	Partner binding
Assay	Structural analysis, Deletion assay, Mutagenesis experiment

AID

472-584 (X-Y linker)

Target domain

318-468 (PI-PLC X domain); 590-706 (PI-PLC Y domain)

Relief mechanism

Partner binding (Heterotrimeric G protein subunits and small GTPase binding at membrane)

Assay

Structural analysis, Deletion assay, Mutagenesis experiment

Target domain	711-719 (Cleft between the TIM barrel and C2 domains of the catalytic core)
Relief mechanism	Partner binding
Assay	Structural analysis, Deletion assay, Mutagenesis experiment

AID

792-805 (Hα2’ helix)

Target domain

711-719 (Cleft between the TIM barrel and C2 domains of the catalytic core)

Relief mechanism

Partner binding (Heterotrimeric G protein subunits and small GTPase binding at membrane)

Assay

Structural analysis, Deletion assay, Mutagenesis experiment

Accessory elements

No accessory elements

References

Hicks SN et al. (2008) "General and versatile autoinhibition of PLC isozymes", Molecular cell, 31, 383-94

Lyon AM et al. (2014) "Molecular mechanisms of phospholipase C β3 autoinhibition", Structure (London, England : 1993), 22, 1844-1854

Muralidharan K et al. (2021) "Structure and regulation of phospholipase Cβ and ε at the membrane", Chemistry and physics of lipids, 235, 105050

Charpentier TH et al. (2014) "Membrane-induced allosteric control of phospholipase C-β isozymes", The Journal of biological chemistry, 289, 29545-57

Lyon AM et al. (2011) "An autoinhibitory helix in the C-terminal region of phospholipase C-β mediates Gαq activation", Nature structural & molecular biology, 18, 999-1005

Autoinhibited structure

Activated structure

11 structures for Q01970

Entry ID	Method	Resolution	Chain	Position	Source
4GNK	X-ray	400 A			PDB
4QJ3	X-ray	300 A	B	10-891	PDB
4QJ4	X-ray	330 A	B	10-891	PDB
4QJ5	X-ray	341 A	B	10-891	PDB
7SQ2	X-ray	260 A	B	10-886	PDB
8EMV	EM	360 A	A	10-1234	PDB
8EMW	EM	350 A	A	10-1234	PDB
8EMX	EM	330 A	A	9-1234	PDB
8UQN	EM	340 A	B	10-1234	PDB
8UQO	EM	337 A	Q	10-1234	PDB
AF-Q01970-F1	Predicted				AlphaFoldDB

881 variants for Q01970

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
CA223833779 rs1037364881	2	A>S		No	ClinGen TOPMed gnomAD
rs759075499 CA6071012	2	A>V		No	ClinGen ExAC gnomAD
CA381087027 rs1382051563	4	A>G		No	ClinGen TOPMed gnomAD
CA6071013 rs769667107	6	P>L		No	ClinGen ExAC TOPMed gnomAD
CA381087109 rs1233394546	9	H>R		No	ClinGen TOPMed
rs1295015515 CA381087220	15	P>L		No	ClinGen TOPMed
rs1340811902 CA381087208	15	P>T		No	ClinGen TOPMed
CA381087307 rs1378481851	21	T>N		No	ClinGen gnomAD
CA381087333 rs1394017988	24	R>C		No	ClinGen TOPMed
CA381087375 rs1467766703	26	S>R		No	ClinGen gnomAD
rs1170974546 CA381087445	30	K>E		No	ClinGen gnomAD
rs183622724 CA223833798	30	K>I		No	ClinGen 1000Genomes TOPMed gnomAD
rs183622724 CA381087454	30	K>R		No	ClinGen 1000Genomes TOPMed gnomAD
CA381087451 rs183622724	30	K>T		No	ClinGen 1000Genomes TOPMed gnomAD
rs189178959 CA6071015	33	E>Q		No	ClinGen 1000Genomes ExAC
rs745355121 CA6071029	35	T>A		No	ClinGen ExAC gnomAD
CA223835507 rs1035422005	37	S>C		No	ClinGen Ensembl
CA381088090 rs769333186	38	R>G		No	ClinGen ExAC TOPMed gnomAD
CA381088095 rs1387966146	38	R>Q		No	ClinGen TOPMed gnomAD
CA6071030 rs769333186	38	R>W		No	ClinGen ExAC TOPMed gnomAD
rs992764519 CA223835514	39	N>K		No	ClinGen Ensembl
rs1281020644 CA381088148	41	V>M		No	ClinGen gnomAD
rs1219072075 COSM1241586 CA381088184	44	R>C	oesophagus large_intestine [Cosmic]	No	ClinGen cosmic curated gnomAD
CA6071031 COSM930043 rs775400340	44	R>H	endometrium [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
CA381088192 rs775400340	44	R>L		No	ClinGen ExAC TOPMed gnomAD
rs111961110 CA6071032	48	N>S		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA381088297 rs1203753995	49	G>C		No	ClinGen gnomAD
CA381088319 rs1489525743	50	F>C		No	ClinGen TOPMed gnomAD
rs773979044 CA6071034	55	T>M		No	ClinGen ExAC TOPMed gnomAD
rs1478264705 CA381088454	57	P>S		No	ClinGen gnomAD
rs761692401 CA6071035	58	N>S		No	ClinGen ExAC gnomAD
rs970082213 CA223835545	58	N>Y		No	ClinGen Ensembl
rs996744728 CA223835781	61	V>A		No	ClinGen TOPMed
rs996744728 CA381089154	61	V>G		No	ClinGen TOPMed
rs1354538033 CA381089160	62	D>E		No	ClinGen TOPMed gnomAD
CA6071056 rs760924697	62	D>N		No	ClinGen ExAC gnomAD
CA223835797 rs1013750320	63	T>I		No	ClinGen gnomAD
CA223835811 rs755175580	65	D>E		No	ClinGen Ensembl
CA381089176 rs1446621016	65	D>G		No	ClinGen gnomAD
rs1555060410 CA381089194	68	S>T		No	ClinGen Ensembl
CA381089214 rs1173164975	71	D>H		No	ClinGen TOPMed
CA6071061 rs753283091	73	R>Q		No	ClinGen ExAC gnomAD
CA381089229 rs1183543027	73	R>W		No	ClinGen TOPMed gnomAD
COSM429524 rs371998747 CA6071062	76	R>Q	breast [Cosmic]	No	ClinGen cosmic curated ESP ExAC TOPMed gnomAD
CA223835830 rs1024183789	76	R>W		No	ClinGen TOPMed
rs764499162 CA6071063	77	Y>N		No	ClinGen ExAC gnomAD
CA223835863 rs989533116	78	A>T		No	ClinGen TOPMed
rs369122916 CA6071067	81	P>T		No	ClinGen ESP ExAC gnomAD
rs1336044037 CA381089275	82	K>Q		No	ClinGen gnomAD
CA6071081 rs751880650	84	P>S		No	ClinGen ExAC TOPMed gnomAD
COSM1298361 CA6071083 rs765986868	87	R>Q	urinary_tract [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
CA6071082 rs201041817	87	R>W		No	ClinGen ExAC TOPMed gnomAD
CA381089341 rs1437235804	90	L>M		No	ClinGen gnomAD
CA6071085 rs754434189	93	G>R		No	ClinGen ExAC gnomAD
rs1223343963 CA381089363	93	G>V		No	ClinGen gnomAD
rs1591100495 CA381089366	94	G>C		No	ClinGen Ensembl
rs143389743 CA6071086	94	G>D		No	ClinGen ESP ExAC TOPMed gnomAD
CA381089371 rs1320367191	95	P>S		No	ClinGen gnomAD
CA6071088 rs758373860	96	D>N		No	ClinGen ExAC TOPMed gnomAD
rs1436761041 CA381089388	97	A>V		No	ClinGen TOPMed gnomAD
rs746775656 CA6071090	98	R>L		No	ClinGen ExAC TOPMed gnomAD
rs746775656 CA223836028	98	R>Q		No	ClinGen ExAC TOPMed gnomAD
rs777872410 CA6071089	98	R>W		No	ClinGen ExAC TOPMed gnomAD
COSM1220915 CA6071093 rs540937471	105	T>M	large_intestine [Cosmic]	No	ClinGen cosmic curated 1000Genomes ExAC TOPMed gnomAD
CA381089623 rs1395650902	107	V>L		No	ClinGen gnomAD
CA381089699 rs1406077648	110	P>S		No	ClinGen gnomAD
COSM1676136 CA6071096 rs769921677	112	P>L	haematopoietic_and_lymphoid_tissue [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
CA6071095 rs769921677	112	P>Q		No	ClinGen ExAC TOPMed gnomAD
rs1591100615 CA381089789	113	V>G		No	ClinGen Ensembl
rs1404574950 CA381089777	113	V>M		No	ClinGen gnomAD
rs772667527 CA223836096	121	M>V		No	ClinGen gnomAD
rs1591100655 CA381090062	123	V>G		No	ClinGen Ensembl
CA6071098 rs769130781	123	V>M		No	ClinGen ExAC gnomAD
rs1469338114 CA381090158	127	T>P		No	ClinGen TOPMed
rs762160886 CA6071100	128	A>V		No	ClinGen ExAC gnomAD
rs1382669550 CA381090394	132	S>F		No	ClinGen gnomAD
CA381090467 rs1451358863	136	F>V		No	ClinGen gnomAD
rs1236447852 CA381090608	140	M>I		No	ClinGen gnomAD
rs1429653849 CA381090596	140	M>T		No	ClinGen gnomAD
CA381090576 rs1347367176	140	M>V		No	ClinGen TOPMed
rs751127522 CA6071131	147	A>T		No	ClinGen ExAC gnomAD
rs965422130 CA223836514	149	R>Q		No	ClinGen gnomAD
CA381090813 rs1460812056	149	R>W		No	ClinGen gnomAD
rs757194151 CA6071132	151	T>S		No	ClinGen ExAC gnomAD
CA6071135 rs755903072	154	R>C		No	ClinGen ExAC TOPMed gnomAD
CA6071136 rs780320976	154	R>H		No	ClinGen ExAC TOPMed gnomAD
rs975881210 CA223836546	155	K>R		No	ClinGen Ensembl
COSM930045 CA6071137 rs144191345	156	A>V	endometrium [Cosmic]	No	ClinGen cosmic curated 1000Genomes ESP ExAC TOPMed gnomAD
CA6071162 COSM3687470 rs199645363 RCV000924033	158	T>M	large_intestine [Cosmic]	No	ClinGen cosmic curated ClinVar 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
CA381091033 rs199645363	158	T>R		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs199897508 CA223836702	160	L>P		No	ClinGen 1000Genomes
CA6071164 rs374487328	163	Q>L		No	ClinGen ESP ExAC TOPMed gnomAD
CA6071163 rs374487328	163	Q>R		No	ClinGen ESP ExAC TOPMed gnomAD
rs368752162 CA223836722	166	Q>H		No	ClinGen ESP TOPMed
CA6071166 rs746266307	169	R>Q		No	ClinGen ExAC gnomAD
CA6071165 rs138400940	169	R>W		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA381091192 rs1292600324	170	I>T		No	ClinGen gnomAD
CA223836738 rs267603096	171	P>L		No	ClinGen gnomAD
rs267603096 CA381091203	171	P>R		No	ClinGen gnomAD
rs150574710 CA381091207	172	V>F		No	ClinGen ESP TOPMed
CA223836743 rs150574710	172	V>I		No	ClinGen ESP TOPMed
CA6071184 rs376722661	181	A>T		No	ClinGen ESP ExAC TOPMed gnomAD
CA223836839 rs1027846634	183	K>Q		No	ClinGen TOPMed
CA223836847 rs952332405	184	K>M		No	ClinGen TOPMed
rs773409515 CA223836851	185	R>W		No	ClinGen Ensembl
CA223836858 rs965741301	186	V>A		No	ClinGen Ensembl
rs983693830 CA223836873	188	T>S		No	ClinGen TOPMed
rs1184780584 CA381091563	189	A>T		No	ClinGen gnomAD
CA6071187 rs771762676	189	A>V		No	ClinGen ExAC gnomAD
CA381091604 rs1278781452	193	C>R		No	ClinGen TOPMed
rs1591101523 CA381091654	196	K>E		No	ClinGen Ensembl
CA381091705 rs1591101534	198	N>T		No	ClinGen Ensembl
rs1160771553 CA381091728	199	R>Q		No	ClinGen gnomAD
rs1400937484 CA381091726	199	R>W		No	ClinGen TOPMed gnomAD
rs1317920964 CA381091788	200	S>N		No	ClinGen gnomAD
CA6071225 rs756651006	201	E>K		No	ClinGen ExAC gnomAD
rs1411785038 CA381091816	204	R>Q		No	ClinGen gnomAD
rs766933332 CA6071226	204	R>W		No	ClinGen ExAC gnomAD
CA6071229 rs777291186	215	R>Q		No	ClinGen ExAC TOPMed gnomAD
COSM317885 CA223837246 rs930346762	215	R>W	lung endometrium [Cosmic]	No	ClinGen cosmic curated Ensembl
CA6071230 rs746737184	218	N>S		No	ClinGen ExAC gnomAD
rs780611720 CA381091949	224	P>L		No	ClinGen ExAC TOPMed gnomAD
rs780611720 CA6071232	224	P>Q		No	ClinGen ExAC TOPMed gnomAD
rs1222807862 CA381091987	229	I>M		No	ClinGen gnomAD
rs1232722708 CA381092010	233	I>T		No	ClinGen gnomAD
CA381092025 rs1316539069	234	G>S		No	ClinGen gnomAD
rs1461712734 CA381092069	240	Y>C		No	ClinGen gnomAD
CA6071262 rs760836389	242	T>M		No	ClinGen ExAC TOPMed gnomAD
rs760018421 CA6071265	244	E>Q		No	ClinGen ExAC gnomAD
CA6071266 rs765691655	247	M>R		No	ClinGen ExAC gnomAD
rs1365732076 CA381092110	247	M>V		No	ClinGen gnomAD
CA381092122 rs1407212405	248	D>E		No	ClinGen gnomAD
rs149333155 CA6071267	248	D>N		No	ClinGen ESP ExAC TOPMed gnomAD
rs1335255056 CA381092130	249	F>L		No	ClinGen gnomAD
rs763355011 CA6071268	250	I>M		No	ClinGen ExAC TOPMed gnomAD
CA381092136 rs1399472388	250	I>T		No	ClinGen gnomAD
CA381092151 rs1337150384	252	Q>H		No	ClinGen gnomAD
CA6071270 rs61734557	252	Q>R		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs755565949 CA6071271	253	K>R		No	ClinGen ExAC TOPMed gnomAD
rs779550854 CA6071272	255	R>C		No	ClinGen ExAC gnomAD
rs753319464 CA6071273	255	R>H		No	ClinGen ExAC gnomAD
rs1205510242 CA381092177	256	D>A		No	ClinGen gnomAD
CA381092172 rs1192999978	256	D>N		No	ClinGen TOPMed
CA381092181 rs916502605	257	P>A		No	ClinGen TOPMed gnomAD
rs1196436813 CA381092183	257	P>L		No	ClinGen gnomAD
CA223837956 rs916502605	257	P>S		No	ClinGen TOPMed gnomAD
rs1181657108 COSM930047 CA381092206	261	E>K	endometrium [Cosmic]	No	ClinGen cosmic curated gnomAD
rs747174251 CA6071279	264	Y>*		No	ClinGen ExAC gnomAD
CA6071278 rs778131119	264	Y>S		No	ClinGen ExAC gnomAD
rs771059102 CA6071280	265	P>L		No	ClinGen ExAC TOPMed gnomAD
CA223838000 rs1049565385	266	P>S		No	ClinGen TOPMed
CA381092246 rs745954606	268	R>G		No	ClinGen ExAC TOPMed gnomAD
rs745954606 CA6071282	268	R>W		No	ClinGen ExAC TOPMed gnomAD
CA223838013 rs909277851	269	P>A		No	ClinGen TOPMed gnomAD
CA381092265 rs1430933423	271	Q>R		No	ClinGen TOPMed
rs770309709 CA6071283	273	R>Q		No	ClinGen ExAC TOPMed gnomAD
CA6071286 rs764499154 COSM1176680	277	E>K	endometrium [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
CA6071287 rs764499154	277	E>Q		No	ClinGen ExAC TOPMed gnomAD
rs765971013 CA6071289	284	Q>R		No	ClinGen ExAC gnomAD
rs754487691 CA6071291	288	R>Q		No	ClinGen ExAC gnomAD
rs1297583271 CA381092401	290	Q>*		No	ClinGen gnomAD
CA223838175 rs111471971	294	E>G		No	ClinGen Ensembl
rs766025514 CA6071308	295	G>S		No	ClinGen ExAC TOPMed gnomAD
CA381092458 rs1171180741	297	S>I		No	ClinGen TOPMed
rs759076306 CA6071310	298	R>C		No	ClinGen ExAC gnomAD
rs764785826 CA6071311	298	R>H		No	ClinGen ExAC gnomAD
rs1001803425 CA223838196	302	G>S		No	ClinGen Ensembl
rs751345085 CA6071315	303	E>A		No	ClinGen ExAC gnomAD
CA381092490 rs1447194242	303	E>K		No	ClinGen TOPMed gnomAD
CA381092541 rs1565331106	309	P>H		No	ClinGen Ensembl
rs554380791 CA6071317	309	P>S		No	ClinGen 1000Genomes ExAC gnomAD
rs143997731 CA6071319	310	L>V		No	ClinGen ESP ExAC TOPMed gnomAD
rs749393152 CA6071321	312	A>T		No	ClinGen ExAC gnomAD
CA6071322 rs769130561	314	D>N		No	ClinGen ExAC gnomAD
rs966112396 CA223838244	316	S>T		No	ClinGen Ensembl
CA6071323 rs372605260	317	T>M		No	ClinGen ESP ExAC TOPMed gnomAD
rs773642415 CA6071326	320	T>P		No	ClinGen ExAC gnomAD
CA381092887 rs1218365880	331	S>*		No	ClinGen gnomAD
rs1464842869 CA381093916	333	N>K		No	ClinGen gnomAD
CA6071332 rs751515672	337	T>A		No	ClinGen ExAC gnomAD
CA381094227 rs1405908704	342	A>T		No	ClinGen gnomAD
CA6071364 rs779837194	346	S>L		No	ClinGen ExAC gnomAD
rs1277317788 CA381094255	347	V>L		No	ClinGen gnomAD
CA381094274 COSM1730520 rs1398585545	349	M>I	liver [Cosmic]	No	ClinGen cosmic curated TOPMed
CA6071366 rs748890795	351	R>C		No	ClinGen ExAC gnomAD
CA381094286 rs748890795	351	R>S		No	ClinGen ExAC gnomAD
rs1482637216 CA381094292	352	Q>*		No	ClinGen gnomAD
CA381094340 COSM930050 rs1192862173	359	R>H	large_intestine endometrium [Cosmic]	No	ClinGen cosmic curated TOPMed
CA381094349 rs941694561	360	C>*		No	ClinGen TOPMed gnomAD
CA381094408 rs1166999822	369	R>W		No	ClinGen gnomAD
rs202112716 CA6071370	370	P>L		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA6071372 rs760447479	371	P>S		No	ClinGen ExAC gnomAD
rs929120823 CA223841322	375	P>L		No	ClinGen TOPMed gnomAD
CA381094472 rs929120823	375	P>R		No	ClinGen TOPMed gnomAD
rs1271246505 CA381094469	375	P>S		No	ClinGen gnomAD
rs1341018158 CA381094525	380	G>S		No	ClinGen gnomAD
CA381094608 rs1349918042	386	E>D		No	ClinGen gnomAD
CA381094620 rs1591105843	387	V>G		No	ClinGen Ensembl
rs759711349 CA6071375	388	P>A		No	ClinGen ExAC gnomAD
rs765514797 CA6071376	388	P>H		No	ClinGen ExAC gnomAD
rs1449612809 CA381094662	390	R>H		No	ClinGen gnomAD
rs758548996 CA381094672	391	D>H		No	ClinGen ExAC TOPMed gnomAD
rs758548996 CA6071378	391	D>N		No	ClinGen ExAC TOPMed gnomAD
CA6071382 rs530167219	398	E>D		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs1039380142 CA223841380	398	E>K		No	ClinGen TOPMed
CA6071383 rs746266616 COSM1220914	404	S>L	large_intestine [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
COSM544305 rs778667804 CA6071385	405	P>A	lung [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
CA6071386 rs747606768	406	Y>F		No	ClinGen ExAC gnomAD
CA6071387 rs771668873	407	P>L		No	ClinGen ExAC
rs1391458784 CA381094898	407	P>S		No	ClinGen gnomAD
CA6071388 rs145872781	408	V>I		No	ClinGen ESP ExAC TOPMed gnomAD
CA6071390 rs770882924	413	E>K		No	ClinGen ExAC gnomAD
rs776358095 CA6071391	415	H>R		No	ClinGen ExAC gnomAD
CA6071394 rs371015701	418	S>L		No	ClinGen ESP ExAC gnomAD
rs765350654 CA6071393	418	S>P		No	ClinGen ExAC TOPMed gnomAD
CA6071414 rs775163753	423	A>E		No	ClinGen ExAC gnomAD
rs769691362 CA6071413	423	A>T		No	ClinGen ExAC TOPMed gnomAD
rs1285886213 CA381096325	425	M>T		No	ClinGen TOPMed
CA6071415 COSM193984 rs141811797	430	R>C	large_intestine [Cosmic]	No	ClinGen cosmic curated 1000Genomes ESP ExAC TOPMed gnomAD
CA381096462 rs141811797	430	R>G		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA6071416 rs769032228	430	R>H		No	ClinGen ExAC TOPMed gnomAD
rs576970524 CA6071418	432	I>V		No	ClinGen 1000Genomes ExAC gnomAD
CA6071420 rs201844304	434	G>E		No	ClinGen ExAC gnomAD
rs761098368 CA6071421	435	D>N		No	ClinGen ExAC gnomAD
CA381096593 rs1181902881	436	A>V		No	ClinGen TOPMed gnomAD
CA6071425 rs777447734	439	I>M		No	ClinGen ExAC TOPMed gnomAD
CA381096636 rs1261558001	439	I>T		No	ClinGen gnomAD
CA381096629 rs1244482152	439	I>V		No	ClinGen Ensembl
rs781098247 CA6071428	440	E>K		No	ClinGen ExAC gnomAD
rs1465082903 CA381096648	440	E>V		No	ClinGen gnomAD
CA6071429 rs745764109	443	D>N		No	ClinGen ExAC
rs936000547 CA223841789	446	P>L		No	ClinGen TOPMed gnomAD
rs769625063 CA6071430	446	P>S		No	ClinGen ExAC gnomAD
rs748312608 CA6071452	448	A>V		No	ClinGen ExAC TOPMed gnomAD
CA381096807 rs1313569981	449	P>T		No	ClinGen TOPMed gnomAD
CA6071455 rs747104158	451	V>I		No	ClinGen ExAC TOPMed gnomAD
rs747104158 CA381096826	451	V>L		No	ClinGen ExAC TOPMed gnomAD
rs1261950958 CA381096834	452	P>L		No	ClinGen TOPMed
CA381096832 rs1265157477	452	P>S		No	ClinGen gnomAD
rs113728113 CA223841970	457	Q>K		No	ClinGen Ensembl
CA6071457 rs777068333	457	Q>R		No	ClinGen ExAC gnomAD
CA381096912 rs1463296496	458	D>A		No	ClinGen gnomAD
rs1413907987 CA381096959	460	M>I		No	ClinGen gnomAD
CA6071459 rs765532483	461	G>C		No	ClinGen ExAC gnomAD
CA381096962 rs765532483	461	G>S		No	ClinGen ExAC gnomAD
CA6071460 rs775839820	462	R>C		No	ClinGen ExAC TOPMed gnomAD
rs1417153759 CA381096987	462	R>H		No	ClinGen TOPMed gnomAD
rs767101293 CA381097130	470	R>W		No	ClinGen ExAC TOPMed gnomAD
CA381097145 rs1434673503	471	H>Y		No	ClinGen gnomAD
CA223842013 rs370417429	472	R>*		No	ClinGen ESP gnomAD
rs749927988 CA6071463	472	R>Q		No	ClinGen ExAC gnomAD
rs753770952 CA6071466	475	A>T		No	ClinGen ExAC TOPMed gnomAD
CA381097254 rs1230584686	476	G>C		No	ClinGen gnomAD
rs1214642777 CA381097283	477	G>D		No	ClinGen gnomAD
rs778809575 CA6071468	477	G>S		No	ClinGen ExAC gnomAD
rs1237762439 CA381097296	478	P>S		No	ClinGen gnomAD
rs1483940368 CA381097321	479	D>Y		No	ClinGen gnomAD
CA6071469 rs747975479	480	S>G		No	ClinGen ExAC gnomAD
rs758622779 CA6071470	480	S>N		No	ClinGen ExAC
rs747103702 CA381097385	481	A>P		No	ClinGen ExAC TOPMed gnomAD
rs747103702 CA6071472	481	A>T		No	ClinGen ExAC TOPMed gnomAD
rs1400270568 CA381097415	482	G>E		No	ClinGen gnomAD
CA6071474 rs776789278	482	G>R		No	ClinGen ExAC TOPMed gnomAD
rs1400270568 CA381097412	482	G>V		No	ClinGen gnomAD
CA381097422 rs1361175878	483	R>C		No	ClinGen gnomAD
rs12146487 VAR_029229 CA6071475	483	R>H		No	ClinGen UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
rs1312390896 CA381097453	485	R>G		No	ClinGen TOPMed gnomAD
rs377744691 CA6071476	485	R>Q		No	ClinGen ESP ExAC TOPMed gnomAD
rs1312390896 CA381097457	485	R>W		No	ClinGen TOPMed gnomAD
CA6071477 rs775784483	487	L>P		No	ClinGen ExAC gnomAD
CA381097554 rs1189681171	490	S>G		No	ClinGen TOPMed
CA223842077 rs935888899	490	S>N		No	ClinGen TOPMed gnomAD
rs1313630930 CA381097578	490	S>R		No	ClinGen gnomAD
CA6071478 rs763359018	491	N>K		No	ClinGen ExAC gnomAD
CA6071479 rs370822360	492	S>F		No	ClinGen ESP ExAC TOPMed gnomAD
rs1184263931 CA381097602	493	A>T		No	ClinGen gnomAD
rs1184723545 CA381097627	495	S>N		No	ClinGen TOPMed
CA6071481 rs760388325	496	E>G		No	ClinGen ExAC gnomAD
CA6071480 rs559883981	496	E>K		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs765740506 CA6071482	497	S>R		No	ClinGen ExAC TOPMed gnomAD
CA6071483 rs753428543	498	S>P		No	ClinGen ExAC TOPMed gnomAD
rs1371253121 CA381097692	498	S>Y		No	ClinGen gnomAD
CA381097712 rs1045784810	499	A>P		No	ClinGen TOPMed
CA223842099 rs1045784810	499	A>T		No	ClinGen TOPMed
CA223842105 rs866502828	499	A>V		No	ClinGen TOPMed gnomAD
CA6071489 rs370491975	502	E>K		No	ClinGen ESP ExAC TOPMed gnomAD
CA6071490 rs370491975	502	E>Q		No	ClinGen ESP ExAC TOPMed gnomAD
rs1301978846 CA381097832	504	S>C		No	ClinGen gnomAD
rs781211293 CA381097847	505	S>C		No	ClinGen ExAC TOPMed gnomAD
rs781211293 CA6071491	505	S>F		No	ClinGen ExAC TOPMed gnomAD
rs745972692 CA6071492	506	P>L		No	ClinGen ExAC TOPMed gnomAD
rs1272356442 CA381097863	506	P>S		No	ClinGen TOPMed gnomAD
CA381097873 rs1248260223	507	Q>K		No	ClinGen TOPMed gnomAD
CA381098099 rs750473868	509	G>A		No	ClinGen ExAC gnomAD
rs750473868 CA6071509	509	G>E		No	ClinGen ExAC gnomAD
rs756253988 CA6071510	510	S>F		No	ClinGen ExAC gnomAD
rs986572757 CA223843015	510	S>P		No	ClinGen Ensembl
CA381098185 rs1203618792	512	S>R		No	ClinGen gnomAD
CA381098237 rs1261378550	515	S>N		No	ClinGen TOPMed gnomAD
CA223843029 rs912029877	517	P>A		No	ClinGen Ensembl
rs769237342 CA6071513	519	L>P		No	ClinGen ExAC gnomAD
CA381098407 rs1236195612	521	N>S		No	ClinGen TOPMed gnomAD
CA6071514 rs779096700	522	G>R		No	ClinGen ExAC gnomAD
rs1169292900 CA381098471	523	E>D		No	ClinGen TOPMed
CA381098452 rs1387879432	523	E>K		No	ClinGen TOPMed
rs748593271 CA6071515	525	V>I		No	ClinGen ExAC TOPMed gnomAD
rs770673792 CA6071516	526	G>R		No	ClinGen ExAC gnomAD
rs776490341 CA6071517	529	K>N		No	ClinGen ExAC TOPMed gnomAD
CA223843077 rs1040353375	529	K>R		No	ClinGen TOPMed
rs745354348 CA6071518	530	P>A		No	ClinGen ExAC gnomAD
rs201842672 CA6071519	531	S>I		No	ClinGen ExAC TOPMed gnomAD
rs775147918 CA6071520	532	L>V		No	ClinGen ExAC gnomAD
CA6071521 rs762763674	534	P>L		No	ClinGen ExAC gnomAD
CA381098650 rs1258173670	534	P>S		No	ClinGen TOPMed
rs764117594 CA6071522	535	Q>R		No	ClinGen ExAC TOPMed gnomAD
CA381098710 rs1352092361 COSM384599	537	S>C	lung [Cosmic]	No	ClinGen cosmic curated gnomAD
CA381098724 rs1236686919	538	L>P		No	ClinGen gnomAD
CA381098742 rs1259224338	539	G>D		No	ClinGen gnomAD
rs946710922 CA223843139	540	D>G		No	ClinGen Ensembl
rs767723592 CA6071525	541	E>K		No	ClinGen ExAC TOPMed gnomAD
rs767723592 CA223843157	541	E>Q		No	ClinGen ExAC TOPMed gnomAD
rs1485596424 CA381098782	542	G>S		No	ClinGen TOPMed gnomAD
rs750702491 CA6071526	544	N>K		No	ClinGen ExAC TOPMed gnomAD
CA6071527 rs756343750	545	R>*		No	ClinGen ExAC gnomAD
CA381098828 rs756343750	545	R>G		No	ClinGen ExAC gnomAD
CA381098838 rs1181594850 COSM3935560	545	R>Q	oesophagus [Cosmic]	No	ClinGen cosmic curated gnomAD
rs1042742836 CA223843172	547	P>H		No	ClinGen Ensembl
CA6071528 rs769830266	548	Y>C		No	ClinGen ExAC TOPMed gnomAD
CA6071530 rs755416443	550	L>H		No	ClinGen ExAC gnomAD
CA6071531 rs755416443	550	L>P		No	ClinGen ExAC gnomAD
rs758887623 CA6071533	551	G>R		No	ClinGen ExAC gnomAD
rs1565334043 CA381098974	553	A>T		No	ClinGen Ensembl
CA381098981 rs1308547507	553	A>V		No	ClinGen gnomAD
CA381099013 rs1372382040	555	R>C		No	ClinGen gnomAD
CA6071534 rs778292336	555	R>H		No	ClinGen ExAC TOPMed gnomAD
CA223843210 rs370692562	558	E>K		No	ClinGen ESP
rs939404151 CA223843234	560	E>A		No	ClinGen Ensembl
CA381099182 rs1160906039	561	D>Y		No	ClinGen TOPMed
CA223843253 rs756540170	562	E>G		No	ClinGen Ensembl
rs117874826 CA6071536	564	E>A		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs769605030 CA6071537	564	E>D		No	ClinGen ExAC
CA381099246 rs1411377909	564	E>K		No	ClinGen gnomAD
rs774816141 CA6071538	566	E>A		No	ClinGen ExAC
CA381099329 rs1369820863	567	Q>H		No	ClinGen gnomAD
CA381099343 rs145777645	568	T>I		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA6071540 rs145777645	568	T>R		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA6071539 rs748881297	568	T>S		No	ClinGen ExAC gnomAD
CA381099383 rs1591108380	570	P>L		No	ClinGen Ensembl
rs1347231387 CA381099378	570	P>S		No	ClinGen gnomAD
rs898455800 CA223843333	571	K>R		No	ClinGen TOPMed
rs1565334129 CA381099470	574	T>I		No	ClinGen Ensembl
CA6071541 rs749020146	574	T>P		No	ClinGen ExAC TOPMed gnomAD
CA381099480 rs1479964063	575	T>A		No	ClinGen gnomAD
CA223844650 rs951456441	581	S>G		No	ClinGen Ensembl
CA381101209 rs1215465391 COSM930052	583	E>K	endometrium [Cosmic]	No	ClinGen cosmic curated gnomAD
rs760502495 CA6071562	587	T>A		No	ClinGen ExAC gnomAD
rs771050979 CA6071563	592	T>K		No	ClinGen ExAC gnomAD
CA381101478 rs771050979	592	T>M		No	ClinGen ExAC gnomAD
CA6071565 rs759688481	594	V>D		No	ClinGen ExAC gnomAD
rs373608404 CA6071568	597	I>M		No	ClinGen ESP ExAC TOPMed gnomAD
CA6071567 rs752754976	597	I>V		No	ClinGen ExAC TOPMed gnomAD
rs1272966818 CA381101717	600	V>I		No	ClinGen gnomAD
rs143280611 CA6071570	603	K>E		No	ClinGen ESP ExAC TOPMed gnomAD
rs779559742 CA6071572	605	F>Y		No	ClinGen ExAC gnomAD
CA223844750 rs975288380	606	E>A		No	ClinGen gnomAD
CA6071573 rs753474990	609	R>*		No	ClinGen ExAC gnomAD
CA6071574 rs754593540	609	R>Q		No	ClinGen ExAC gnomAD
CA6071592 rs753119736	611	R>K		No	ClinGen ExAC TOPMed gnomAD
CA6071594 rs754635618	612	N>K		No	ClinGen ExAC gnomAD
CA223845065 rs915651305	613	K>R		No	ClinGen TOPMed gnomAD
CA223845076 rs931020922	614	C>R		No	ClinGen TOPMed
rs1418743509 CA381102312	620	F>I		No	ClinGen gnomAD
rs1401093153 CA381102342	621	V>A		No	ClinGen TOPMed
rs757958118 CA6071597	623	T>P		No	ClinGen ExAC gnomAD
rs1377354341 CA381102395	624	K>R		No	ClinGen gnomAD
rs746878888 CA6071599	626	M>T		No	ClinGen ExAC TOPMed gnomAD
rs777274459 CA6071598	626	M>V		No	ClinGen ExAC TOPMed gnomAD
CA381102455 rs1371760533	627	E>V		No	ClinGen gnomAD
rs1447560766 CA381102509	630	T>A		No	ClinGen gnomAD
CA381102518 rs1420679798	630	T>S		No	ClinGen TOPMed
CA6071601 rs780995372	632	S>N		No	ClinGen ExAC gnomAD
CA6071603 rs770031431	634	M>T		No	ClinGen ExAC gnomAD
rs1349404174 CA381102619	635	E>G		No	ClinGen gnomAD
rs1565335153 CA381102657	637	V>E		No	ClinGen Ensembl
rs749366365 CA6071605	638	E>A		No	ClinGen ExAC TOPMed gnomAD
CA223845163 rs1045333166	638	E>K		No	ClinGen TOPMed gnomAD
rs748215865 CA6071626	639	Y>*		No	ClinGen ExAC gnomAD
rs1311495551 CA381102756	639	Y>H		No	ClinGen TOPMed
rs1199338461 CA381102795	641	K>R		No	ClinGen TOPMed gnomAD
CA6071628 rs773649985	642	Q>K		No	ClinGen ExAC gnomAD
COSM930054 rs777008773 CA6071631	653	R>H	endometrium [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
CA6071633 rs763787385	654	V>M		No	ClinGen ExAC TOPMed gnomAD
rs751051176 CA6071634	660	M>I		No	ClinGen ExAC gnomAD
rs540587716 CA6071635	662	Q>H		No	ClinGen 1000Genomes ExAC gnomAD
rs1332868773 CA381103072	666	N>S		No	ClinGen gnomAD
rs1486749917 CA381103087	667	V>A		No	ClinGen TOPMed
rs901228245 CA223845599	667	V>I		No	ClinGen gnomAD
rs901228245 CA381103083	667	V>L		No	ClinGen gnomAD
rs1195240043 CA381103096	668	G>R		No	ClinGen TOPMed
CA381103151 rs1448789256	672	V>A		No	ClinGen gnomAD
rs1337526589 CA381103158	673	A>T		No	ClinGen TOPMed
rs753709749 CA6071640	679	L>F		No	ClinGen ExAC TOPMed gnomAD
CA6071664 rs527496239	681	V>M		No	ClinGen 1000Genomes ExAC gnomAD
rs969729562 CA223846040	682	A>V		No	ClinGen Ensembl
rs1236649489 CA381103416	687	A>T		No	ClinGen gnomAD
rs369907605 CA6071667	687	A>V		No	ClinGen ESP ExAC TOPMed gnomAD
rs772576811 COSM3375899 CA6071671	689	V>I	pancreas [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
rs1264309392 CA381103488	692	Y>N		No	ClinGen TOPMed
rs746961549 CA6071673	694	G>R		No	ClinGen ExAC TOPMed gnomAD
CA6071674 COSM3687472 rs776651979	695	R>C	large_intestine [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
CA6071675 rs759550537	695	R>H		No	ClinGen ExAC gnomAD
rs1301364795 CA381103679	706	R>Q		No	ClinGen gnomAD
CA6071680 rs751637404 COSM1676138	706	R>W	haematopoietic_and_lymphoid_tissue [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
COSM75972 rs1228790993 CA381103682	707	R>Q	ovary [Cosmic]	No	ClinGen cosmic curated gnomAD
COSM1355656 CA381103681 rs1347713381	707	R>W	large_intestine [Cosmic]	No	ClinGen cosmic curated gnomAD
rs757389231 CA381103686	708	P>A		No	ClinGen ExAC gnomAD
CA6071682 rs377220651	708	P>L		No	ClinGen ESP ExAC TOPMed gnomAD
rs757389231 CA6071681	708	P>S		No	ClinGen ExAC gnomAD
CA381103704 rs1591111391	709	D>G		No	ClinGen Ensembl
CA223846173 rs865911130	711	S>F		No	ClinGen Ensembl
CA381103826 rs1591111427	713	D>A		No	ClinGen Ensembl
CA6071685 rs780232749	713	D>H		No	ClinGen ExAC TOPMed gnomAD
COSM4146055 CA6071686 rs780232749	713	D>N	thyroid [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
rs771594751 CA6071687	714	P>A		No	ClinGen ExAC gnomAD
CA381103915 rs746671277	717	E>A		No	ClinGen ExAC gnomAD
CA6071689 rs746671277	717	E>G		No	ClinGen ExAC gnomAD
CA6071690 rs145953984	719	I>M		No	ClinGen ESP ExAC TOPMed gnomAD
rs776311793 CA6071691	720	V>M		No	ClinGen ExAC TOPMed gnomAD
CA381104054 rs1395429625	723	I>N		No	ClinGen gnomAD
rs759493346 CA6071692	723	I>V		No	ClinGen ExAC gnomAD
rs1591111488 CA381104071	724	V>M		No	ClinGen Ensembl
CA381104116 rs1483393827	725	A>V		No	ClinGen TOPMed
CA6071696 rs372978072	729	R>Q		No	ClinGen ESP ExAC TOPMed gnomAD
rs781050534 CA6071695	729	R>W		No	ClinGen ExAC TOPMed gnomAD
CA6071713 rs370898239	732	V>M		No	ClinGen ESP ExAC TOPMed gnomAD
rs182388407 CA223846365	739	S>F		No	ClinGen 1000Genomes
rs774167540 CA6071715	740	D>N		No	ClinGen ExAC TOPMed gnomAD
rs774167540 CA223846382	740	D>Y		No	ClinGen ExAC TOPMed gnomAD
CA6071716 rs761974335	741	R>K		No	ClinGen ExAC TOPMed gnomAD
CA381104613 rs1355633997	744	G>S		No	ClinGen gnomAD
rs767776666 CA6071717	745	I>T		No	ClinGen ExAC gnomAD
CA381104729 rs1258197895	749	V>L		No	ClinGen gnomAD
rs774505582 CA223846407	751	M>L		No	ClinGen TOPMed
CA223846413 rs1001241446	751	M>T		No	ClinGen Ensembl
rs1238319926 CA381104838	752	F>C		No	ClinGen TOPMed
CA223846414 rs1027325697	754	L>I		No	ClinGen Ensembl
CA223846423 rs887956650	756	V>I		No	ClinGen TOPMed
CA6071719 rs760877917	758	T>M		No	ClinGen ExAC gnomAD
rs755470901 COSM1676139 CA381105009	759	R>W	large_intestine [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
CA6071723 rs201470515	760	R>C		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA6071724 rs556404139	760	R>H		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA6071725 rs556404139	760	R>L		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA6071726 rs781055740	763	R>C		No	ClinGen ExAC TOPMed gnomAD
CA223846513 rs976957731	765	R>P		No	ClinGen Ensembl
rs1006609373 CA223846502	765	R>W		No	ClinGen TOPMed
CA381105245 rs1223995593	768	Q>R		No	ClinGen gnomAD
CA6071731 rs749213059	771	S>L		No	ClinGen ExAC gnomAD
rs745918779 CA223846597	775	V>M		No	ClinGen gnomAD
CA6071737 rs371358482	777	D>E		No	ClinGen ESP ExAC TOPMed gnomAD
CA6071736 rs371358482	777	D>E		No	ClinGen ESP ExAC TOPMed gnomAD
CA6071738 rs766440947	778	E>K		No	ClinGen ExAC TOPMed gnomAD
rs760061612 CA6071740	782	D>N		No	ClinGen ExAC gnomAD
rs1188751860 CA381105685	784	P>S		No	ClinGen gnomAD
CA223846624 rs1049675387	785	K>R		No	ClinGen TOPMed
rs1591112655 CA381106049	786	V>G		No	ClinGen Ensembl
rs1433734734 CA381106072	789	P>L		No	ClinGen gnomAD
CA381106077 rs1424867148	790	T>M		No	ClinGen TOPMed
rs1591112696 CA381106094	793	S>L		No	ClinGen Ensembl
CA223847369 rs901529250	795	R>C		No	ClinGen Ensembl
CA223847372 rs997197383	796	I>V		No	ClinGen Ensembl
CA223847374 rs979093622	797	A>T		No	ClinGen TOPMed
CA223847380 rs774110238	797	A>V		No	ClinGen Ensembl
rs764515580 CA6071761	798	A>T		No	ClinGen ExAC TOPMed gnomAD
CA381106124 rs1271887863	799	F>V		No	ClinGen gnomAD
CA6071762 rs751892571	802	G>A		No	ClinGen ExAC gnomAD
CA381106161 rs1591112761	804	K>R		No	ClinGen Ensembl
rs370452345 CA6071764	806	V>A		No	ClinGen ESP ExAC gnomAD
RCV000969796 rs145502455 CA6071763	806	V>I		No	ClinGen ClinVar 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
CA381106186 rs1591112776	808	H>P		No	ClinGen Ensembl
rs1204585395 CA381106189	808	H>Q		No	ClinGen TOPMed gnomAD
CA223847402 rs935071157	810	I>L		No	ClinGen TOPMed gnomAD
CA381106199 rs1591112802	810	I>T		No	ClinGen Ensembl
rs1243151945 CA381106213	813	V>I		No	ClinGen gnomAD
CA381106221 rs1185079538	814	S>A		No	ClinGen gnomAD
CA6071766 rs754544025	814	S>F		No	ClinGen ExAC gnomAD
CA6071767 rs778397140	815	A>P		No	ClinGen ExAC gnomAD
CA6071769 rs199676501	817	R>C		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs1403053840 CA381106238	817	R>H		No	ClinGen gnomAD
CA6071790 rs372712260	823	V>I		No	ClinGen ESP ExAC TOPMed gnomAD
rs377311495 CA381106364	827	N>K		No	ClinGen ESP ExAC TOPMed gnomAD
rs1379549050 CA381106383	828	E>D		No	ClinGen gnomAD
CA381106452 rs1251623441	831	Q>H		No	ClinGen TOPMed
CA381106453 rs1251623441	831	Q>H		No	ClinGen TOPMed
rs749423527 CA6071794	832	P>L		No	ClinGen ExAC gnomAD
rs1175517846 CA381106462	832	P>S		No	ClinGen gnomAD
CA223847541 rs971412836	834	C>F		No	ClinGen gnomAD
CA381106493 rs971412836	834	C>Y		No	ClinGen gnomAD
CA223847554 COSM1355658 rs142407686	836	P>L	large_intestine [Cosmic]	No	ClinGen cosmic curated ESP
rs1315106612 CA381106542	837	A>T		No	ClinGen TOPMed
rs373726563 CA223847579 COSM930057	843	E>K	endometrium [Cosmic]	No	ClinGen cosmic curated ESP TOPMed
rs35169799 CA6071800	845	S>L		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA6071803 rs200176343	848	I>V		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA6071805 rs369369040	851	D>N		No	ClinGen ESP ExAC TOPMed gnomAD
rs1277140660 CA381106846	854	D>E		No	ClinGen gnomAD
CA6071806 rs757251970	854	D>H		No	ClinGen ExAC TOPMed gnomAD
COSM930058 rs758823609 CA6071833	856	A>V	endometrium haematopoietic_and_lymphoid_tissue [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
CA381106875 rs1487909591	857	E>K		No	ClinGen TOPMed gnomAD
CA6071838 rs748845467	866	V>I		No	ClinGen ExAC TOPMed gnomAD
CA223847950 rs1010470631	868	L>P		No	ClinGen TOPMed gnomAD
rs1255664242 CA381107072	873	A>T		No	ClinGen gnomAD
CA6071840 rs772766671	873	A>V		No	ClinGen ExAC gnomAD
CA6071841 rs761453570	874	R>G		No	ClinGen ExAC TOPMed gnomAD
CA6071842 rs767552332	874	R>Q		No	ClinGen ExAC TOPMed gnomAD
rs761453570 CA381107080	874	R>W		No	ClinGen ExAC TOPMed gnomAD
CA381107096 rs1195550688	875	Q>K		No	ClinGen TOPMed
CA6071845 rs760695903	878	A>S		No	ClinGen ExAC TOPMed gnomAD
COSM3687473 CA6071844 rs760695903	878	A>T	large_intestine [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
rs1355621620 CA381107145	878	A>V		No	ClinGen gnomAD
rs1310207881 CA381107152	879	L>F		No	ClinGen gnomAD
rs1320567116 CA381107165	880	I>F		No	ClinGen TOPMed gnomAD
rs1320567116 CA381107167	880	I>L		No	ClinGen TOPMed gnomAD
CA6071846 rs200263631	880	I>T		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs1320567116 CA381107163	880	I>V		No	ClinGen TOPMed gnomAD
CA223847987 rs1129384	881	G>E		No	ClinGen gnomAD
CA381107208 rs1215541955	882	E>G		No	ClinGen gnomAD
CA6071847 rs755122025	883	S>T		No	ClinGen ExAC gnomAD
rs1229112177 CA381107241	884	E>K		No	ClinGen TOPMed
CA223850938 rs541577872	885	A>T		No	ClinGen Ensembl
rs1259670240 CA381108705	885	A>V		No	ClinGen TOPMed
CA6071870 rs764110243	887	A>T		No	ClinGen ExAC gnomAD
CA381108804 rs1465815196	890	E>G		No	ClinGen gnomAD
CA6071871 rs751688786	890	E>Q		No	ClinGen ExAC gnomAD
CA6071874 rs199593049	891	T>K		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA6071873 rs199593049	891	T>M		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA6071876 rs780290101	892	C>S		No	ClinGen ExAC TOPMed gnomAD
CA6071878 rs771875912	893	Q>P		No	ClinGen ExAC
CA6071879 rs777384185	895	T>I		No	ClinGen ExAC gnomAD
CA381108922 rs1241450021	896	Q>P		No	ClinGen gnomAD
CA381108969 rs1591114676	899	Q>H		No	ClinGen Ensembl
CA381108974 rs1300333348	900	L>P		No	ClinGen gnomAD
rs776569909 CA6071882	901	G>A		No	ClinGen ExAC TOPMed gnomAD
CA6071883 rs759395988	903	Q>R		No	ClinGen ExAC TOPMed gnomAD
rs141905815 CA6071884	904	P>L		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs1457346376 CA381109040	904	P>S		No	ClinGen gnomAD
rs763137823 CA6071886	905	S>C		No	ClinGen ExAC gnomAD
rs373585561 CA6071890	909	T>I		No	ClinGen ESP ExAC TOPMed gnomAD
rs766978565 CA6071888	909	T>P		No	ClinGen ExAC TOPMed gnomAD
rs373585561 CA6071889	909	T>S		No	ClinGen ESP ExAC TOPMed gnomAD
CA381109136 rs1371545781	910	P>S		No	ClinGen TOPMed
CA381109182 rs1430884960	911	S>N		No	ClinGen gnomAD
rs1335160164 CA381109167	911	S>R		No	ClinGen TOPMed gnomAD
CA381109189 rs1430884960	911	S>T		No	ClinGen gnomAD
CA381109209 rs756613164	912	P>A		No	ClinGen ExAC TOPMed
CA6071892 rs756613164	912	P>S		No	ClinGen ExAC TOPMed
CA381109224 rs1323665307	913	L>P		No	ClinGen gnomAD
CA381109225 rs1323665307	913	L>R		No	ClinGen gnomAD
rs906047792 CA223851050	914	D>N		No	ClinGen TOPMed gnomAD
rs1351483262 CA381109267	915	A>T		No	ClinGen gnomAD
rs1434201855 CA381109285	915	A>V		No	ClinGen gnomAD
rs1292923210 CA381109302	916	S>C		No	ClinGen gnomAD
CA381109304 rs1292923210	916	S>F		No	ClinGen gnomAD
rs754291794 CA6071894	916	S>P		No	ClinGen ExAC gnomAD
CA381109345 rs758116241	917	P>H		No	ClinGen ExAC TOPMed gnomAD
CA6071895 rs758116241	917	P>L		No	ClinGen ExAC TOPMed gnomAD
rs746669193 CA6071897	918	R>C		No	ClinGen ExAC TOPMed
rs746669193 CA381109370	918	R>G		No	ClinGen ExAC TOPMed
rs770407468 CA6071898	918	R>H		No	ClinGen ExAC TOPMed gnomAD
rs770407468 CA223851103	918	R>P		No	ClinGen ExAC TOPMed gnomAD
CA381109430 rs769667587	919	R>P		No	ClinGen ExAC TOPMed gnomAD
rs769667587 CA6071901	919	R>Q		No	ClinGen ExAC TOPMed gnomAD
rs745768031 CA6071900	919	R>W		No	ClinGen ExAC TOPMed gnomAD
rs538437430 RCV000980068 CA6071902	920	P>H		No	ClinGen ClinVar 1000Genomes ExAC TOPMed dbSNP gnomAD
CA6071903 rs762804403	921	P>H		No	ClinGen ExAC gnomAD
CA381109538 rs1191983605	923	P>L		No	ClinGen TOPMed gnomAD
CA381109540 rs1591114948	924	T>P		No	ClinGen Ensembl
rs1038218211 CA223851171	925	T>P		No	ClinGen Ensembl
rs1591114962 CA381109584	926	S>P		No	ClinGen Ensembl
CA381109610 rs1477295630	927	P>A		No	ClinGen TOPMed gnomAD
rs774500063 CA6071905	927	P>L		No	ClinGen ExAC gnomAD
CA223851188 rs774500063	927	P>R		No	ClinGen ExAC gnomAD
rs1477295630 CA381109615	927	P>T		No	ClinGen TOPMed gnomAD
CA381109621 rs1394121034	928	A>T		No	ClinGen TOPMed
rs762031101 CA6071906	928	A>V		No	ClinGen ExAC gnomAD
rs1403143454 CA381109648	929	S>G		No	ClinGen gnomAD
CA381109689 rs1322774323	930	T>I		No	ClinGen TOPMed gnomAD
CA381109722 rs1401563176	932	L>V		No	ClinGen gnomAD
CA6071909 rs761226304	934	S>T		No	ClinGen ExAC gnomAD
rs766860169 CA6071910	935	P>R		No	ClinGen ExAC gnomAD
CA381109861 rs1286224919	936	G>R		No	ClinGen TOPMed gnomAD
rs1238588959 CA381109982	937	Q>*		No	ClinGen gnomAD
rs760721647 CA6071927	938	R>C		No	ClinGen ExAC TOPMed gnomAD
rs766576084 CA6071928	938	R>H		No	ClinGen ExAC
CA223851326 rs766576084	938	R>L		No	ClinGen ExAC
rs1350066784 CA381110021	939	D>E		No	ClinGen gnomAD
rs1346108792 CA381110010	939	D>H		No	ClinGen gnomAD
CA6071929 rs777208047	940	D>E		No	ClinGen ExAC gnomAD
CA223851344 rs777208047	940	D>E		No	ClinGen ExAC gnomAD
CA381110034 rs1202581747	940	D>Y		No	ClinGen gnomAD
rs1440348995 CA381110049	941	L>F		No	ClinGen gnomAD
rs1238246666 CA381110084	943	A>T		No	ClinGen gnomAD
rs749978087 CA6071952	949	V>A		No	ClinGen ExAC TOPMed gnomAD
rs749978087 CA381110294	949	V>G		No	ClinGen ExAC TOPMed gnomAD
rs79573066 CA6071951	949	V>M		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs988857946 CA223851519	951	P>A		No	ClinGen TOPMed gnomAD
CA6071953 rs760408690	951	P>H		No	ClinGen ExAC TOPMed gnomAD
rs765829193 CA6071954	952	T>N		No	ClinGen ExAC gnomAD
CA381110347 rs1196777013	952	T>P		No	ClinGen TOPMed
rs981845851 CA223851553	953	P>L		No	ClinGen gnomAD
CA6071958 rs752690042	956	E>K		No	ClinGen ExAC TOPMed gnomAD
rs1380367315 CA381110444	957	L>F		No	ClinGen TOPMed gnomAD
CA381110440 rs1380367315	957	L>I		No	ClinGen TOPMed gnomAD
rs960193376 CA381110463	958	R>P		No	ClinGen TOPMed gnomAD
CA223851580 rs960193376	958	R>Q		No	ClinGen TOPMed gnomAD
rs777651285 CA6071960	959	G>D		No	ClinGen ExAC TOPMed gnomAD
rs1390675083 CA381110469	959	G>S		No	ClinGen gnomAD
rs1300440757 CA381110522	962	A>T		No	ClinGen gnomAD
rs1281164636 CA381110536	963	L>V		No	ClinGen TOPMed
rs1338998769 CA381110592	966	L>F		No	ClinGen gnomAD
CA381110595 rs1225536348	966	L>P		No	ClinGen TOPMed
rs145650860 CA381110603	967	R>L		No	ClinGen ESP ExAC TOPMed gnomAD
rs145650860 CA6071961	967	R>Q		No	ClinGen ESP ExAC TOPMed gnomAD
CA381110598 rs1591115604	967	R>W		No	ClinGen Ensembl
rs771325943 CA381110631	968	S>R		No	ClinGen ExAC gnomAD
CA6071962 rs771325943	968	S>R		No	ClinGen ExAC gnomAD
CA6071964 rs746011802	969	R>Q		No	ClinGen ExAC TOPMed gnomAD
CA6071963 rs781389205	969	R>W		No	ClinGen ExAC TOPMed gnomAD
CA381110671 rs1263558702	971	E>K		No	ClinGen gnomAD
CA381110688 rs1216988104	972	R>Q		No	ClinGen TOPMed gnomAD
CA6071966 rs775803752	975	R>Q		No	ClinGen ExAC TOPMed gnomAD
rs548243845 CA223851668 COSM1475705	975	R>W	breast [Cosmic]	No	ClinGen cosmic curated 1000Genomes gnomAD
rs929342331 CA223851700	978	R>C		No	ClinGen TOPMed gnomAD
rs1385082928 CA381110776	978	R>H		No	ClinGen gnomAD
CA6071970 rs774803533	982	Q>*		No	ClinGen ExAC gnomAD
CA6071969 rs774803533	982	Q>E		No	ClinGen ExAC gnomAD
CA381110855 rs1419520120	983	R>Q		No	ClinGen gnomAD
rs766064640 CA6071971	983	R>W		No	ClinGen ExAC gnomAD
rs754752866 CA223851741	985	A>S		No	ClinGen Ensembl
rs1051794098 CA223851746	987	T>A		No	ClinGen gnomAD
rs1379476989 CA381110943	987	T>N		No	ClinGen TOPMed gnomAD
CA6071973 rs753345370	990	R>C		No	ClinGen ExAC TOPMed gnomAD
rs764803222 CA6071974	990	R>H		No	ClinGen ExAC gnomAD
rs753345370 CA6071972	990	R>S		No	ClinGen ExAC TOPMed gnomAD
CA6071975 rs778035486	991	R>H		No	ClinGen ExAC TOPMed gnomAD
rs778035486 CA381111069	991	R>L		No	ClinGen ExAC TOPMed gnomAD
rs866153827 CA223851797	997	A>D		No	ClinGen gnomAD
CA381111186 rs866153827	997	A>G		No	ClinGen gnomAD
rs1260944340 CA381111169	997	A>T		No	ClinGen TOPMed
rs1180404124 CA381111233	998	Q>H		No	ClinGen gnomAD
CA6071978 rs751408753	998	Q>K		No	ClinGen ExAC gnomAD
CA381111238 rs1242593624	999	A>T		No	ClinGen TOPMed gnomAD
CA223851826 rs1039253489	1000	Q>L		No	ClinGen TOPMed gnomAD
CA6071979 rs142330950	1002	E>D		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA381111353 rs1418817618	1003	G>S		No	ClinGen gnomAD
rs1591115826 CA381111401	1005	C>G		No	ClinGen Ensembl
rs1467258981 CA381111414	1006	R>Q		No	ClinGen gnomAD
rs781621157 CA6071980	1006	R>W		No	ClinGen ExAC TOPMed gnomAD
rs752015281 CA6071982	1008	R>Q		No	ClinGen ExAC gnomAD
rs746102181 CA6071981	1008	R>W		No	ClinGen ExAC gnomAD
CA381111491 rs1301713462	1009	P>L		No	ClinGen gnomAD
CA381111511 rs1313795310	1010	G>D		No	ClinGen gnomAD
rs1370182058 CA381111496	1010	G>S		No	ClinGen gnomAD
rs61757725 CA381111701	1013	G>D		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA6072003 rs61757725	1013	G>V		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs1338793509 CA381111716	1015	A>T		No	ClinGen gnomAD
CA381111723 rs1228994606	1015	A>V		No	ClinGen gnomAD
CA6072006 rs772383000	1016	A>T		No	ClinGen ExAC TOPMed gnomAD
CA381111760 rs1222486691	1017	D>A		No	ClinGen gnomAD
CA381111763 rs1222486691	1017	D>G		No	ClinGen gnomAD
rs745495212 CA6072008	1018	V>M		No	ClinGen ExAC TOPMed gnomAD
rs1175447128 CA381111816	1020	D>N		No	ClinGen TOPMed
CA6072009 rs138821310	1021	T>M		No	ClinGen ESP ExAC TOPMed gnomAD
CA6072010 rs138821310	1021	T>R		No	ClinGen ESP ExAC TOPMed gnomAD
rs762581356 CA6072011	1022	K>R		No	ClinGen ExAC gnomAD
rs148059922 CA6072013	1023	E>D		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA6072012 RCV000968675 rs148059922	1023	E>D		No	ClinGen ClinVar 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
rs750293397 CA381111921	1024	G>A		No	ClinGen ExAC TOPMed gnomAD
CA6072016 rs750293397 COSM84086	1024	G>E	pancreas [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
rs369629062 CA6072015	1024	G>R		No	ClinGen ESP ExAC TOPMed gnomAD
rs369629062 CA381111918	1024	G>R		No	ClinGen ESP ExAC TOPMed gnomAD
rs369629062 CA6072014	1024	G>W		No	ClinGen ESP ExAC TOPMed gnomAD
rs1162919816 CA381111932	1025	E>K		No	ClinGen gnomAD
rs1242860582 CA381112012	1027	E>A		No	ClinGen TOPMed
rs1202156521 CA381112053	1027	E>D		No	ClinGen TOPMed
CA6072018 rs766694013	1027	E>K		No	ClinGen ExAC gnomAD
rs1316444044 CA381112075	1028	A>E		No	ClinGen gnomAD
CA6072021 rs778991743	1030	R>Q		No	ClinGen ExAC TOPMed gnomAD
rs753853049 CA6072020	1030	R>W		No	ClinGen ExAC TOPMed gnomAD
rs758949240 CA6072023	1031	Y>F		No	ClinGen ExAC TOPMed gnomAD
rs748601971 CA6072022	1031	Y>H		No	ClinGen ExAC TOPMed gnomAD
rs1292859527 CA381112160	1032	Q>*		No	ClinGen TOPMed
rs778078363 CA6072024	1033	E>K		No	ClinGen ExAC TOPMed gnomAD
rs1356245504 CA381112246	1034	F>C		No	ClinGen gnomAD
rs1203774867 CA381112261	1035	Q>R		No	ClinGen gnomAD
rs769317676 CA6072026	1036	N>D		No	ClinGen ExAC gnomAD
rs775148939 CA6072027	1039	V>M		No	ClinGen ExAC TOPMed gnomAD
rs1380876837 CA381112395	1040	Q>H		No	ClinGen gnomAD
CA6072028 rs748898547	1040	Q>R		No	ClinGen ExAC gnomAD
rs1441263715 CA381112451	1043	L>M		No	ClinGen gnomAD
CA6072030 rs774022823	1046	R>Q		No	ClinGen ExAC TOPMed gnomAD
CA223852339 rs201285488	1046	R>W		No	ClinGen TOPMed gnomAD
rs543434519 CA6072031	1047	E>K		No	ClinGen 1000Genomes ExAC gnomAD
CA381112601 rs1310566246	1049	Q>H		No	ClinGen TOPMed gnomAD
rs1591116604 CA381112634	1050	V>G		No	ClinGen Ensembl
rs1170583245 CA381112649	1051	D>A		No	ClinGen TOPMed
CA381112664 rs138022371	1051	D>E		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs772178442 CA6072032	1051	D>H		No	ClinGen ExAC gnomAD
rs367679278 CA6072034	1052	A>T		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA381112732 rs1425898333	1054	A>G		No	ClinGen gnomAD
CA6072035 rs766104713	1055	Q>P		No	ClinGen ExAC gnomAD
rs375052596 CA6072037	1056	R>G		No	ClinGen ESP ExAC TOPMed gnomAD
rs1027121213 CA223852391	1056	R>Q		No	ClinGen TOPMed gnomAD
CA6072038 rs375052596	1056	R>W		No	ClinGen ESP ExAC TOPMed gnomAD
rs902360563 CA223852396	1057	R>K		No	ClinGen Ensembl
CA381112878 rs1202509808	1059	E>V		No	ClinGen gnomAD
rs1174490656 CA381112922	1060	H>Q		No	ClinGen gnomAD
rs752811479 CA6072039	1060	H>Y		No	ClinGen ExAC gnomAD
CA223852411 rs750517645	1062	R>T		No	ClinGen Ensembl
rs1026415025 CA223852702	1064	A>D		No	ClinGen gnomAD
rs1181554946 CA381113113	1064	A>P		No	ClinGen TOPMed
rs1218126452 CA381113185	1067	R>Q		No	ClinGen gnomAD
CA6072066 rs566345432	1067	R>W		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA6072067 rs757919733	1069	R>G		No	ClinGen ExAC gnomAD
CA381113282 rs1591116875	1071	V>G		No	ClinGen Ensembl
CA381113301 rs1250630420	1072	V>A		No	ClinGen gnomAD
CA6072069 rs374742247	1072	V>I		No	ClinGen ESP ExAC TOPMed gnomAD
rs770811617 CA6072070	1075	A>T		No	ClinGen ExAC gnomAD
rs769589327 CA6072073	1078	T>A		No	ClinGen ExAC TOPMed gnomAD
CA223852788 rs764552814	1079	Q>E		No	ClinGen Ensembl
rs1284772797 CA381113535	1080	F>Y		No	ClinGen TOPMed
rs1238058299 CA381113579	1082	R>K		No	ClinGen TOPMed
rs1565338782 CA381113802	1088	E>A		No	ClinGen Ensembl
rs367729670 CA6072076	1088	E>K		No	ClinGen ESP ExAC gnomAD
CA6072077 rs367729670	1088	E>Q		No	ClinGen ESP ExAC gnomAD
CA381114065 rs1591117169	1090	E>G		No	ClinGen Ensembl
rs1314970156 CA381114192	1093	E>*		No	ClinGen gnomAD
CA6072106 rs763710295	1093	E>G		No	ClinGen ExAC gnomAD
rs763710295 CA381114218	1093	E>V		No	ClinGen ExAC gnomAD
CA6072107 rs201700958	1095	Q>R		No	ClinGen ExAC TOPMed gnomAD
rs756653717 CA6072108	1096	K>R		No	ClinGen ExAC gnomAD
rs749911369 CA381114354	1099	D>N		No	ClinGen gnomAD
rs749911369 CA223853016	1099	D>Y		No	ClinGen gnomAD
rs947971788 CA223853028	1102	R>H		No	ClinGen gnomAD
CA381114437 rs947971788	1102	R>L		No	ClinGen gnomAD
CA6072111 rs756092707	1104	N>S		No	ClinGen ExAC gnomAD
CA6072112 rs779793894	1106	I>M		No	ClinGen ExAC gnomAD
CA6072113 rs749150328	1107	S>L		No	ClinGen ExAC TOPMed gnomAD
rs1173641781 CA381114609	1109	A>P		No	ClinGen gnomAD
rs1404807598 CA381114619	1109	A>V		No	ClinGen gnomAD
rs1442821717 CA381114630	1110	K>E		No	ClinGen gnomAD
rs1370855685 CA381114794	1115	H>P		No	ClinGen TOPMed gnomAD
rs202061611 CA6072116	1118	E>K		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs772009523 CA6072117	1119	A>V		No	ClinGen ExAC TOPMed gnomAD
rs1565339029 CA381115015	1120	E>*		No	ClinGen Ensembl
rs1565339033 CA381115027	1120	E>V		No	ClinGen Ensembl
CA6072136 rs772390550	1121	L>V		No	ClinGen ExAC gnomAD
CA6072137 rs777990791	1122	T>A		No	ClinGen ExAC gnomAD
rs575846795 CA6072138	1122	T>M		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
COSM3791762 rs575846795 CA6072139	1122	T>R	urinary_tract [Cosmic]	No	ClinGen cosmic curated 1000Genomes ExAC TOPMed gnomAD
rs978162911 CA223853322	1123	E>G		No	ClinGen Ensembl
CA6072141 rs760112482	1123	E>K		No	ClinGen ExAC gnomAD
CA6072142 rs201342752	1126	R>C		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA381115152 rs1268489463	1126	R>H		No	ClinGen gnomAD
rs1247323607 CA381115164	1127	R>Q		No	ClinGen gnomAD
rs1361432461 COSM930060 CA381115160	1127	R>W	endometrium [Cosmic]	No	ClinGen cosmic curated TOPMed gnomAD
CA6072143 rs146026378	1128	H>Y		No	ClinGen ESP ExAC gnomAD
rs1290498415 CA381115303	1134	N>K		No	ClinGen gnomAD
CA381115293 rs1222231802	1134	N>T		No	ClinGen gnomAD
rs767214397 CA6072145	1135	S>F		No	ClinGen ExAC TOPMed gnomAD
CA381115351 rs1254014643	1137	R>C		No	ClinGen gnomAD
rs138542727 CA223853368	1138	R>L		No	ClinGen ESP gnomAD
rs138542727 CA381115366	1138	R>Q		No	ClinGen ESP gnomAD
CA6072146 rs749930140	1138	R>W		No	ClinGen ExAC gnomAD
rs775703680 CA381116905	1140	E>K		No	ClinGen ExAC TOPMed gnomAD
rs775703680 CA6072161	1140	E>Q		No	ClinGen ExAC TOPMed gnomAD
rs1233223236 CA381116965	1141	E>D		No	ClinGen TOPMed gnomAD
CA223853959 rs377316065	1145	Q>R		No	ClinGen ESP TOPMed gnomAD
CA381117120 rs1157007035	1146	R>Q		No	ClinGen TOPMed gnomAD
rs1470305551 CA381117151	1147	H>Y		No	ClinGen gnomAD
CA381117233 rs1404074201	1148	D>G		No	ClinGen gnomAD
CA381117207 rs1178670983	1148	D>N		No	ClinGen gnomAD
CA223853977 rs912212228	1149	R>C		No	ClinGen TOPMed gnomAD
CA381117259 rs1330190396	1149	R>H		No	ClinGen TOPMed gnomAD
CA381117275 rs1337860204	1151	V>M		No	ClinGen gnomAD
rs1440491126 CA381117340	1152	A>V		No	ClinGen gnomAD
CA381117387 rs1591118405	1153	G>A		No	ClinGen Ensembl
rs1277352541 CA381117401	1154	Q>E		No	ClinGen gnomAD
CA223853993 rs1051475415	1157	V>G		No	ClinGen Ensembl
rs141163685 CA6072164	1164	E>D		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs1199775804 CA381117699	1166	P>R		No	ClinGen gnomAD
rs1439289068 CA381117726	1167	K>R		No	ClinGen TOPMed gnomAD
CA381117836 rs1194000869	1170	A>T		No	ClinGen TOPMed gnomAD
CA381117873 rs1374930968	1171	Q>*		No	ClinGen gnomAD
rs1474707956 CA381117913	1172	L>P		No	ClinGen gnomAD
CA6072175 rs757594793	1173	A>S		No	ClinGen ExAC TOPMed gnomAD
rs757594793 CA381117915	1173	A>T		No	ClinGen ExAC TOPMed gnomAD
rs781399407 CA6072176	1173	A>V		No	ClinGen ExAC TOPMed gnomAD
rs1304531766 CA381117987	1174	Q>H		No	ClinGen TOPMed gnomAD
CA6072178 rs756574311	1174	Q>K		No	ClinGen ExAC
rs1363347444 CA381118001	1175	E>Q		No	ClinGen gnomAD
rs562555278 CA6072180	1176	C>F		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs1014045893 CA223854110	1176	C>R		No	ClinGen TOPMed gnomAD
CA381118035 rs1014045893	1176	C>S		No	ClinGen TOPMed gnomAD
rs562555278 CA6072179	1176	C>Y		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs1296819765 CA381118097	1178	E>A		No	ClinGen gnomAD
CA381118086 rs1225109299	1178	E>K		No	ClinGen gnomAD
CA381118111 rs1359823356	1179	Q>K		No	ClinGen gnomAD
CA6072182 rs774726938	1180	R>Q		No	ClinGen ExAC TOPMed gnomAD
CA6072181 rs768957160	1180	R>W		No	ClinGen ExAC TOPMed gnomAD
CA381118154 rs776004312	1181	A>G		No	ClinGen ExAC TOPMed gnomAD
CA6072184 rs770615156	1181	A>T		No	ClinGen ExAC gnomAD
CA6072185 rs776004312	1181	A>V		No	ClinGen ExAC TOPMed gnomAD
CA223854160 rs372161244	1182	R>S		No	ClinGen ESP ExAC TOPMed gnomAD
CA223854153 rs372161244	1182	R>S		No	ClinGen ESP ExAC TOPMed gnomAD
rs1161210162 CA381118200	1183	L>F		No	ClinGen TOPMed gnomAD
rs1162051052 CA381118234	1184	P>H		No	ClinGen gnomAD
rs1162051052 CA381118238	1184	P>L		No	ClinGen gnomAD
CA381118223 rs1446765324	1184	P>S		No	ClinGen gnomAD
CA381118241 rs1368311550	1185	Q>K		No	ClinGen TOPMed gnomAD
rs1019529699 CA223854192	1186	E>Q		No	ClinGen Ensembl
CA381118313 rs763017593	1188	R>C		No	ClinGen ExAC TOPMed gnomAD
rs551386366 CA223854199	1188	R>H		No	ClinGen 1000Genomes TOPMed gnomAD
CA6072190 rs763017593	1188	R>S		No	ClinGen ExAC TOPMed gnomAD
CA6072192 rs751448730	1189	R>Q		No	ClinGen ExAC gnomAD
CA6072191 rs571482177	1189	R>W		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA6072194 rs767845691	1190	S>C		No	ClinGen ExAC
CA381118382 rs750612765	1190	S>R		No	ClinGen ExAC TOPMed gnomAD
rs750612765 CA6072195	1190	S>R		No	ClinGen ExAC TOPMed gnomAD
CA381118438 rs374705748	1193	G>A		No	ClinGen ESP ExAC TOPMed gnomAD
rs374705748 CA6072196	1193	G>V		No	ClinGen ESP ExAC TOPMed gnomAD
CA381118445 rs1348573420	1194	E>K		No	ClinGen gnomAD
CA381118525 rs1244218453	1195	M>I		No	ClinGen gnomAD
CA381118543 rs1393739611	1196	P>A		No	ClinGen TOPMed gnomAD
rs192464486 CA6072197	1196	P>L		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA223854274 rs968847885	1197	E>*		No	ClinGen Ensembl
CA6072199 rs567001401	1197	E>D		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs1420085333 CA381118637	1198	G>E		No	ClinGen gnomAD
CA381118644 rs372053350	1199	L>M		No	ClinGen ESP ExAC TOPMed gnomAD
CA381118660 rs1455122865	1199	L>P		No	ClinGen gnomAD
CA6072202 rs772433905	1201	D>G		No	ClinGen ExAC gnomAD
CA381118769 rs1243495747	1202	G>A		No	ClinGen TOPMed gnomAD
rs1243495747 CA381118762	1202	G>E		No	ClinGen TOPMed gnomAD
CA381118753 rs1334657765	1202	G>R		No	ClinGen gnomAD
CA381118791 rs1378127802	1203	P>L		No	ClinGen gnomAD
CA381118817 rs1309352627	1204	L>P		No	ClinGen TOPMed gnomAD
CA381118796 rs1391785279	1204	L>V		No	ClinGen TOPMed gnomAD
CA381118827 rs1228074362	1205	V>M		No	ClinGen gnomAD
rs1263804546 CA381118853	1206	A>T		No	ClinGen gnomAD
rs1325800558 CA381118879	1206	A>V		No	ClinGen gnomAD
CA381118927 rs774904091	1207	C>F		No	ClinGen ExAC TOPMed gnomAD
CA6072206 rs774904091	1207	C>S		No	ClinGen ExAC TOPMed gnomAD
CA381118936 rs1481130850	1207	C>W		No	ClinGen gnomAD
rs1179321174 CA381118992	1208	A>V		No	ClinGen TOPMed gnomAD
CA381119004 rs1375548022	1209	S>N		No	ClinGen TOPMed
CA6072207 rs762962879	1210	N>D		No	ClinGen ExAC gnomAD
CA381119037 rs1181075690	1210	N>S		No	ClinGen TOPMed gnomAD
CA381119033 rs762962879	1210	N>Y		No	ClinGen ExAC gnomAD
CA6072208 rs374008060	1211	G>S		No	ClinGen ExAC TOPMed gnomAD
rs146327074 CA6072211	1213	A>S		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA6072210 rs146327074	1213	A>T		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs1472382083 CA381119175	1214	P>A		No	ClinGen TOPMed
rs760836121 CA6072213	1215	G>R		No	ClinGen ExAC TOPMed gnomAD
CA6072215 rs113554478	1218	G>R		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA381119404 rs1301106059	1219	H>Q		No	ClinGen TOPMed gnomAD
CA6072216 rs755460841	1219	H>R		No	ClinGen ExAC gnomAD
rs1347414657 CA381119375	1219	H>Y		No	ClinGen gnomAD
rs1308593978 CA381119408	1220	L>M		No	ClinGen gnomAD
CA6072217 rs376493974	1221	S>L		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs1482957097 CA381119461	1222	G>S		No	ClinGen gnomAD
CA6072219 rs765843635	1223	A>T		No	ClinGen ExAC TOPMed gnomAD
CA381119526 rs1188960710	1224	D>H		No	ClinGen gnomAD
CA381119523 rs1188960710	1224	D>N		No	ClinGen gnomAD
CA223854424 rs778033643	1225	S>*		No	ClinGen ExAC TOPMed gnomAD
CA6072220 rs778033643	1225	S>L		No	ClinGen ExAC TOPMed gnomAD
CA6072222 rs538389088	1226	E>K		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs779604089 CA6072223	1227	S>I		No	ClinGen ExAC gnomAD
CA381119683 rs779604089	1227	S>T		No	ClinGen ExAC gnomAD
CA223854484 rs1043020383	1229	E>D		No	ClinGen TOPMed gnomAD
CA381119889 rs1367686240	1232	T>M		No	ClinGen gnomAD
rs768286371 CA6072226	1232	T>P		No	ClinGen ExAC gnomAD
rs886939466 CA223854525	1233	Q>H		No	ClinGen TOPMed
CA381119926 rs1293000586	1234	L>F		No	ClinGen gnomAD

1 associated diseases with Q01970

[MIM: 618961]: Spondylometaphyseal dysplasia with corneal dystrophy (SMDCD)

An autosomal recessive disorder characterized by postnatal growth deficiency, profound limb shortening with proximal and distal segments involvement, narrow chest, radiological abnormalities involving the spine, pelvis and metaphyses, corneal clouding, and intellectual disability. {ECO:0000269|PubMed:29122926}. Note=The disease is caused by variants affecting the gene represented in this entry.

Without disease ID

An autosomal recessive disorder characterized by postnatal growth deficiency, profound limb shortening with proximal and distal segments involvement, narrow chest, radiological abnormalities involving the spine, pelvis and metaphyses, corneal clouding, and intellectual disability. {ECO:0000269|PubMed:29122926}. Note=The disease is caused by variants affecting the gene represented in this entry.

6 regional properties for Q01970

Type	Name	Position	InterPro Accession
domain	C2 domain	707 - 835	IPR000008
domain	Phosphatidylinositol-specific phospholipase C, X domain	317 - 469	IPR000909
domain	Phospholipase C, phosphatidylinositol-specific, Y domain	590 - 706	IPR001711
domain	Phospholipase C-beta, C-terminal domain	1029 - 1200	IPR014815
domain	Phosphoinositide-specific phospholipase C, EF-hand-like domain	217 - 308	IPR015359
domain	PLC-beta, PH domain	18 - 149	IPR037862

Functions

		Description
EC Number	3.1.4.11	Phosphoric diester hydrolases
Subcellular Localization	Cytoplasm Membrane Nucleus	And particulate fractions
PANTHER Family	PTHR10336	PHOSPHOINOSITIDE-SPECIFIC PHOSPHOLIPASE C FAMILY PROTEIN
PANTHER Subfamily	PTHR10336:SF11	1-PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE PHOSPHODIESTERASE BETA-3
PANTHER Protein Class	phospholipase
PANTHER Pathway Category	Inflammation mediated by chemokine and cytokine signaling pathway PLCbetagamma Wnt signaling pathway Phospholipase C Thyrotropin-releasing hormone receptor signaling pathway PLC Heterotrimeric G-protein signaling pathway-Gq alpha and Go alpha mediated pathway Phospholipase C-beta 2-arachidonoylglycerol biosynthesis PLC Endogenous cannabinoid signaling PLC Endothelin signaling pathway PLCbeta Alpha adrenergic receptor signaling pathway PLC Oxytocin receptor mediated signaling pathway PLC beta Angiotensin II-stimulated signaling through G proteins and beta-arrestin PLC 5HT2 type receptor mediated signaling pathway PLC Histamine H1 receptor mediated signaling pathway PLC

5 GO annotations of cellular component

Name	Definition
cytosol	The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
membrane	A lipid bilayer along with all the proteins and protein complexes embedded in it an attached to it.
nucleus	A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent.
postsynaptic cytosol	The region of the cytosol consisting of all cytosol that is part of the postsynapse.
protein-containing complex	A stable assembly of two or more macromolecules, i.e. proteins, nucleic acids, carbohydrates or lipids, in which at least one component is a protein and the constituent parts function together.

5 GO annotations of molecular function

Name	Definition
cadherin binding	Binding to cadherin, a type I membrane protein involved in cell adhesion.
calcium ion binding	Binding to a calcium ion (Ca2+).
calmodulin binding	Binding to calmodulin, a calcium-binding protein with many roles, both in the calcium-bound and calcium-free states.
phosphatidylinositol phospholipase C activity	Catalysis of the reaction: 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate + H(2)O = 1,2-diacylglycerol + 1D-myo-inositol 1,4,5-trisphosphate + H(+).
phospholipase C activity	Catalysis of the reaction: a phospholipid + H2O = 1,2-diacylglycerol + a phosphatidate.

5 GO annotations of biological process

Name	Definition
G protein-coupled receptor signaling pathway	The series of molecular signals initiated by a ligand binding to its receptor, in which the activated receptor promotes the exchange of GDP for GTP on the alpha-subunit of an associated heterotrimeric G-protein complex. The GTP-bound activated alpha-G-protein then dissociates from the beta- and gamma-subunits to further transmit the signal within the cell. The pathway begins with receptor-ligand interaction, and ends with regulation of a downstream cellular process. The pathway can start from the plasma membrane, Golgi or nuclear membrane.
lipid catabolic process	The chemical reactions and pathways resulting in the breakdown of lipids, compounds soluble in an organic solvent but not, or sparingly, in an aqueous solvent.
phosphatidylinositol metabolic process	The chemical reactions and pathways involving phosphatidylinositol, any glycophospholipid in which a sn-glycerol 3-phosphate residue is esterified to the 1-hydroxyl group of 1D-myo-inositol.
phosphatidylinositol-mediated signaling	The series of molecular signals in which a cell uses a phosphatidylinositol-mediated signaling to convert a signal into a response. Phosphatidylinositols include phosphatidylinositol (PtdIns) and its phosphorylated derivatives.
regulation of systemic arterial blood pressure	The process that modulates the force with which blood travels through the systemic arterial circulatory system. The process is controlled by a balance of processes that increase pressure and decrease pressure.

27 homologous proteins in AiPD

UniProt AC	Gene Name	Protein Name	Species	Evidence Code
P32383	PLC1	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase 1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)	PR
P10894	PLCB1	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1	Bos taurus (Bovine)	SS
Q15111	PLCL1	Inactive phospholipase C-like protein 1	Homo sapiens (Human)	PR
Q9UPR0	PLCL2	Inactive phospholipase C-like protein 2	Homo sapiens (Human)	PR
Q86YW0	PLCZ1	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase zeta-1	Homo sapiens (Human)	PR
Q8N3E9	PLCD3	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-3	Homo sapiens (Human)	SS
Q9BRC7	PLCD4	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-4	Homo sapiens (Human)	SS
P16885	PLCG2	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2	Homo sapiens (Human)	SS
P19174	PLCG1	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1	Homo sapiens (Human)	EV
Q00722	PLCB2	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2	Homo sapiens (Human)	EV
Q9NQ66	PLCB1	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1	Homo sapiens (Human)	EV
Q9P212	PLCE1	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1	Homo sapiens (Human)	SS
P51178	PLCD1	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-1	Homo sapiens (Human)	EV
Q15147	PLCB4	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4	Homo sapiens (Human)	PR
A3KGF7	Plcb2	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2	Mus musculus (Mouse)	PR
Q9Z1B3	Plcb1	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1	Mus musculus (Mouse)	SS
P51432	Plcb3	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3	Mus musculus (Mouse)	SS
P10687	Plcb1	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1	Rattus norvegicus (Rat)	SS
Q99JE6	Plcb3	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3	Rattus norvegicus (Rat)	SS
G5EBH0	egl-8	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta egl-8	Caenorhabditis elegans	SS
Q8GV43	PLC6	Phosphoinositide phospholipase C 6	Arabidopsis thaliana (Mouse-ear cress)	PR
Q944C2	PLC5	Phosphoinositide phospholipase C 5	Arabidopsis thaliana (Mouse-ear cress)	PR
Q6NMA7	PLC9	Phosphoinositide phospholipase C 9	Arabidopsis thaliana (Mouse-ear cress)	PR
Q9STZ3	PLC8	Phosphoinositide phospholipase C 8	Arabidopsis thaliana (Mouse-ear cress)	PR
Q56W08	PLC3	Phosphoinositide phospholipase C 3	Arabidopsis thaliana (Mouse-ear cress)	PR
Q39032	PLC1	Phosphoinositide phospholipase C 1	Arabidopsis thaliana (Mouse-ear cress)	PR
Q944C1	PLC4	Phosphoinositide phospholipase C 4	Arabidopsis thaliana (Mouse-ear cress)	PR

10	20	30	40	50	60
MAGAQPGVHA	LQLEPPTVVE	TLRRGSKFIK	WDEETSSRNL	VTLRVDPNGF	FLYWTGPNME
70	80	90	100	110	120
VDTLDISSIR	DTRTGRYARL	PKDPKIREVL	GFGGPDARLE	EKLMTVVSGP	DPVNTVFLNF
130	140	150	160	170	180
MAVQDDTAKV	WSEELFKLAM	NILAQNASRN	TFLRKAYTKL	KLQVNQDGRI	PVKNILKMFS
190	200	210	220	230	240
ADKKRVETAL	ESCGLKFNRS	ESIRPDEFSL	EIFERFLNKL	CLRPDIDKIL	LEIGAKGKPY
250	260	270	280	290	300
LTLEQLMDFI	NQKQRDPRLN	EVLYPPLRPS	QARLLIEKYE	PNQQFLERDQ	MSMEGFSRYL
310	320	330	340	350	360
GGEENGILPL	EALDLSTDMT	QPLSAYFINS	SHNTYLTAGQ	LAGTSSVEMY	RQALLWGCRC
370	380	390	400	410	420
VELDVWKGRP	PEEEPFITHG	FTMTTEVPLR	DVLEAIAETA	FKTSPYPVIL	SFENHVDSAK
430	440	450	460	470	480
QQAKMAEYCR	SIFGDALLIE	PLDKYPLAPG	VPLPSPQDLM	GRILVKNKKR	HRPSAGGPDS
490	500	510	520	530	540
AGRKRPLEQS	NSALSESSAA	TEPSSPQLGS	PSSDSCPGLS	NGEEVGLEKP	SLEPQKSLGD
550	560	570	580	590	600
EGLNRGPYVL	GPADREDEEE	DEEEEEQTDP	KKPTTDEGTA	SSEVNATEEM	STLVNYIEPV
610	620	630	640	650	660
KFKSFEAARK	RNKCFEMSSF	VETKAMEQLT	KSPMEFVEYN	KQQLSRIYPK	GTRVDSSNYM
670	680	690	700	710	720
PQLFWNVGCQ	LVALNFQTLD	VAMQLNAGVF	EYNGRSGYLL	KPEFMRRPDK	SFDPFTEVIV
730	740	750	760	770	780
DGIVANALRV	KVISGQFLSD	RKVGIYVEVD	MFGLPVDTRR	KYRTRTSQGN	SFNPVWDEEP
790	800	810	820	830	840
FDFPKVVLPT	LASLRIAAFE	EGGKFVGHRI	LPVSAIRSGY	HYVCLRNEAN	QPLCLPALLI
850	860	870	880	890	900
YTEASDYIPD	DHQDYAEALI	NPIKHVSLMD	QRARQLAALI	GESEAQAGQE	TCQDTQSQQL
910	920	930	940	950	960
GSQPSSNPTP	SPLDASPRRP	PGPTTSPAST	SLSSPGQRDD	LIASILSEVA	PTPLDELRGH
970	980	990	1000	1010	1020
KALVKLRSRQ	ERDLRELRKK	HQRKAVTLTR	RLLDGLAQAQ	AEGRCRLRPG	ALGGAADVED
1030	1040	1050	1060	1070	1080
TKEGEDEAKR	YQEFQNRQVQ	SLLELREAQV	DAEAQRRLEH	LRQALQRLRE	VVLDANTTQF
1090	1100	1110	1120	1130	1140
KRLKEMNERE	KKELQKILDR	KRHNSISEAK	MRDKHKKEAE	LTEINRRHIT	ESVNSIRRLE
1150	1160	1170	1180	1190	1200
EAQKQRHDRL	VAGQQQVLQQ	LAEEEPKLLA	QLAQECQEQR	ARLPQEIRRS	LLGEMPEGLG
1210	1220	1230
DGPLVACASN	GHAPGSSGHL	SGADSESQEE	NTQL