Mutagenetix > Incidental Mutation

Incidental Mutation 'R1657:Scn5a'

186472

Institutional Source

Beutler Lab

Gene Symbol

Scn5a

Ensembl Gene

ENSMUSG00000032511

Gene Name

sodium channel, voltage-gated, type V, alpha

Synonyms

Nav1.5c, Nav1.5, mH1, SkM2

MMRRC Submission

039693-MU

Accession Numbers

Ncbi RefSeq: NM_021544.4, NM_001253860.1; MGI:98251

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R1657 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

119483408-119579016 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 119562380 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Aspartic acid to Glycine at position 82 (D82G)

Ref Sequence

ENSEMBL: ENSMUSP00000113272 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000065196] [ENSMUST00000117911] [ENSMUST00000120420] [ENSMUST00000138934]

AlphaFold

Q9JJV9

Predicted Effect

probably damaging
Transcript: ENSMUST00000065196
AA Change: D82G

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000066228
Gene: ENSMUSG00000032511
AA Change: D82G

Domain	Start	End	E-Value	Type
Pfam:Ion_trans	130	423	2.4e-82	PFAM
Pfam:Na_trans_cytopl	478	667	5.2e-49	PFAM
Pfam:Ion_trans	716	950	1.1e-54	PFAM
Pfam:Na_trans_assoc	955	1203	2.9e-57	PFAM
Pfam:Ion_trans	1207	1484	2e-66	PFAM
Pfam:Ion_trans	1530	1786	7.2e-55	PFAM
Pfam:PKD_channel	1627	1780	3.5e-7	PFAM
IQ	1903	1925	5e-2	SMART
low complexity region	1961	1983	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000117911
AA Change: D82G

PolyPhen 2 Score 0.997 (Sensitivity: 0.41; Specificity: 0.98)

SMART Domains

Protein: ENSMUSP00000112838
Gene: ENSMUSG00000032511
AA Change: D82G

Domain	Start	End	E-Value	Type
Pfam:Ion_trans	159	412	9.6e-76	PFAM
coiled coil region	413	451	N/A	INTRINSIC
Pfam:DUF3451	461	668	4.9e-44	PFAM
Pfam:Ion_trans	751	940	2.3e-46	PFAM
Pfam:Na_trans_assoc	955	1218	1.2e-73	PFAM
Pfam:Ion_trans	1244	1472	2e-56	PFAM
PDB:1BYY\|A	1474	1526	5e-29	PDB
Pfam:Ion_trans	1565	1774	1.5e-49	PFAM
Pfam:PKD_channel	1627	1781	2.6e-10	PFAM
IQ	1903	1925	5e-2	SMART
low complexity region	1961	1983	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000120420
AA Change: D82G

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000113272
Gene: ENSMUSG00000032511
AA Change: D82G

Domain	Start	End	E-Value	Type
Pfam:Ion_trans	159	412	4.5e-75	PFAM
coiled coil region	413	451	N/A	INTRINSIC
Pfam:DUF3451	461	668	7.4e-43	PFAM
Pfam:Ion_trans	751	940	1.2e-45	PFAM
Pfam:Na_trans_assoc	955	1217	1.6e-72	PFAM
Pfam:Ion_trans	1243	1471	1.1e-55	PFAM
PDB:1BYY\|A	1473	1525	5e-29	PDB
Pfam:Ion_trans	1564	1773	8.2e-49	PFAM
Pfam:PKD_channel	1626	1780	2.6e-9	PFAM
IQ	1902	1924	5e-2	SMART
low complexity region	1960	1982	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000138934

Coding Region Coverage

1x: 99.1%
3x: 98.4%
10x: 96.5%
20x: 93.2%

Validation Efficiency

MGI Phenotype

Strain: 2179753; 3765977
Lethality: E10-E12
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene is an integral membrane protein and tetrodotoxin-resistant voltage-gated sodium channel subunit. This protein is found primarily in cardiac muscle and is responsible for the initial upstroke of the action potential in an electrocardiogram. Defects in this gene are a cause of long QT syndrome type 3 (LQT3), an autosomal dominant cardiac disease. Alternative splicing results in several transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]
PHENOTYPE: Mice homozygous for mutations in this gene die prenatally usually during organogenesis and may display decreased embryo size and abnormal cardiovascular system physiology. Heterozygous mice typically display abnormal heartbeats and defects in the function of the impulse conduction system. [provided by MGI curators]

Allele List at MGI

All alleles(11) : Targeted(9) Gene trapped(2)

Other mutations in this stock

Total: 55 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
0610009B22Rik	T	C	11: 51,685,678	Q131R	probably benign	Het
3632451O06Rik	G	C	14: 49,773,560	T230S	probably damaging	Het
Acaca	T	G	11: 84,264,084	D988E	probably benign	Het
Als2	A	G	1: 59,180,601	V1185A	probably damaging	Het
Amdhd2	A	G	17: 24,156,055	V391A	probably damaging	Het
Caprin1	A	T	2: 103,769,506	V608E	probably damaging	Het
Celsr3	T	A	9: 108,842,952	C2512*	probably null	Het
Cfl1	A	T	19: 5,493,555	R187W	probably damaging	Het
Cgnl1	C	T	9: 71,725,944	V42I	probably damaging	Het
Chd2	A	G	7: 73,480,430	Y826H	probably damaging	Het
Col9a2	C	A	4: 121,040,974	P28T	unknown	Het
Cyp3a44	G	A	5: 145,779,743	P346S	probably damaging	Het
Dact2	A	G	17: 14,197,990	V151A	probably benign	Het
Dhx29	T	C	13: 112,952,843	I716T	probably damaging	Het
Esam	T	C	9: 37,537,621	S342P	probably damaging	Het
Fam189a2	C	A	19: 23,975,635	C437F	probably damaging	Het
Fer1l4	A	G	2: 156,035,598	V1053A	possibly damaging	Het
Grk3	A	G	5: 112,966,982	F124S	probably damaging	Het
H2-DMa	G	A	17: 34,137,399		probably null	Het
Hsd3b5	T	A	3: 98,619,720	I137F	possibly damaging	Het
Itgav	A	T	2: 83,801,779	I902F	probably benign	Het
Itsn1	G	T	16: 91,909,223	C179F	probably damaging	Het
Kcnh8	G	A	17: 52,839,125	R347H	probably damaging	Het
Kif9	T	C	9: 110,489,966	M166T	possibly damaging	Het
Kmt5c	C	T	7: 4,746,454	Q324*	probably null	Het
Lcn9	G	A	2: 25,824,710	E154K	probably benign	Het
Mfge8	A	T	7: 79,141,773	L227Q	probably benign	Het
Mroh2b	A	T	15: 4,931,043	R753*	probably null	Het
Mtif2	G	A	11: 29,540,721	R475Q	probably benign	Het
Nln	C	T	13: 104,036,947	V584I	possibly damaging	Het
Nr2e3	T	C	9: 59,948,767	E129G	probably benign	Het
Ocstamp	T	C	2: 165,397,516	D250G	probably damaging	Het
Olfr1065	A	C	2: 86,445,218	L255V	probably damaging	Het
Olfr403	A	T	11: 74,195,896	H131L	probably damaging	Het
Olfr503	T	C	7: 108,545,377	I284T	possibly damaging	Het
Pld1	A	T	3: 28,071,187	I417L	probably benign	Het
Polr1a	A	T	6: 71,941,535	K692N	probably damaging	Het
Qsox2	A	T	2: 26,220,747	Y152*	probably null	Het
Rpap1	T	C	2: 119,783,778	D46G	possibly damaging	Het
Rpe65	A	G	3: 159,614,448	T246A	probably damaging	Het
Sema3d	A	G	5: 12,584,974	E669G	possibly damaging	Het
Serpinb6c	T	C	13: 33,880,226	N282S	probably benign	Het
Snap47	A	T	11: 59,428,770	S181T	probably benign	Het
Snx9	A	C	17: 5,918,436	T336P	possibly damaging	Het
Sphkap	G	A	1: 83,277,515	R838*	probably null	Het
Terb1	A	T	8: 104,488,491	D284E	possibly damaging	Het
Tmem266	C	T	9: 55,418,008	A153V	probably damaging	Het
Ttn	T	C	2: 76,742,804	E25915G	possibly damaging	Het
Tubal3	A	G	13: 3,933,011	T264A	possibly damaging	Het
Vldlr	G	A	19: 27,245,670	R747Q	probably benign	Het
Zc3h8	G	T	2: 128,929,957		probably benign	Het
Zfp184	C	T	13: 21,959,273	T383M	probably damaging	Het
Zfp455	T	C	13: 67,198,639	F38S	possibly damaging	Het
Zfp746	A	G	6: 48,082,174	V167A	possibly damaging	Het
Zfp985	T	A	4: 147,584,110	N478K	probably benign	Het

Other mutations in Scn5a

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00336:Scn5a	APN	9	119486224	missense	probably damaging	1.00
IGL00480:Scn5a	APN	9	119517538	missense	possibly damaging	0.73
IGL00542:Scn5a	APN	9	119492126	missense	probably damaging	1.00
IGL00852:Scn5a	APN	9	119537682	missense	probably benign	0.26
IGL00895:Scn5a	APN	9	119513104	splice site	probably null
IGL00905:Scn5a	APN	9	119536501	missense	probably damaging	1.00
IGL01347:Scn5a	APN	9	119562441	nonsense	probably null
IGL01396:Scn5a	APN	9	119534704	missense	probably damaging	0.98
IGL01402:Scn5a	APN	9	119486470	missense	probably damaging	1.00
IGL01404:Scn5a	APN	9	119486470	missense	probably damaging	1.00
IGL01487:Scn5a	APN	9	119562623	start codon destroyed	probably null	0.90
IGL01612:Scn5a	APN	9	119486025	missense	possibly damaging	0.86
IGL02134:Scn5a	APN	9	119485892	missense	probably damaging	0.98
IGL02434:Scn5a	APN	9	119533793	missense	possibly damaging	0.83
IGL02698:Scn5a	APN	9	119521097	missense	probably damaging	1.00
IGL02717:Scn5a	APN	9	119529010	missense	probably benign	0.12
IGL02746:Scn5a	APN	9	119550637	missense	probably damaging	1.00
IGL02951:Scn5a	APN	9	119495685	missense	probably damaging	1.00
IGL03155:Scn5a	APN	9	119512182	missense	possibly damaging	0.74
IGL03188:Scn5a	APN	9	119522566	missense	probably damaging	1.00
IGL03268:Scn5a	APN	9	119521231	missense	probably damaging	1.00
IGL03287:Scn5a	APN	9	119489778	missense	probably damaging	1.00
IGL03328:Scn5a	APN	9	119537636	missense	probably benign	0.12
PIT4142001:Scn5a	UTSW	9	119486258	missense	probably damaging	1.00
PIT4520001:Scn5a	UTSW	9	119534570	missense	possibly damaging	0.56
R0026:Scn5a	UTSW	9	119522566	missense	probably damaging	1.00
R0044:Scn5a	UTSW	9	119492047	critical splice donor site	probably null
R0044:Scn5a	UTSW	9	119492047	critical splice donor site	probably null
R0267:Scn5a	UTSW	9	119543135	missense	probably damaging	0.98
R0313:Scn5a	UTSW	9	119534571	missense	probably damaging	1.00
R0360:Scn5a	UTSW	9	119522599	missense	probably damaging	0.99
R0364:Scn5a	UTSW	9	119522599	missense	probably damaging	0.99
R0369:Scn5a	UTSW	9	119533772	missense	probably damaging	0.99
R0512:Scn5a	UTSW	9	119550658	missense	probably damaging	1.00
R0681:Scn5a	UTSW	9	119539640	missense	probably damaging	0.96
R1163:Scn5a	UTSW	9	119533927	missense	probably damaging	1.00
R1469:Scn5a	UTSW	9	119533661	critical splice donor site	probably null
R1469:Scn5a	UTSW	9	119533661	critical splice donor site	probably null
R1470:Scn5a	UTSW	9	119536475	missense	possibly damaging	0.82
R1470:Scn5a	UTSW	9	119536475	missense	possibly damaging	0.82
R1530:Scn5a	UTSW	9	119495562	missense	probably damaging	1.00
R1532:Scn5a	UTSW	9	119533847	missense	probably damaging	1.00
R1544:Scn5a	UTSW	9	119486633	missense	probably damaging	1.00
R1588:Scn5a	UTSW	9	119521301	missense	probably damaging	1.00
R1597:Scn5a	UTSW	9	119562497	missense	probably damaging	0.99
R1607:Scn5a	UTSW	9	119486092	missense	probably damaging	1.00
R1664:Scn5a	UTSW	9	119521177	missense	possibly damaging	0.84
R1785:Scn5a	UTSW	9	119521129	missense	probably damaging	1.00
R1925:Scn5a	UTSW	9	119529019	missense	probably benign
R1956:Scn5a	UTSW	9	119517413	missense	possibly damaging	0.82
R2006:Scn5a	UTSW	9	119536480	missense	probably damaging	1.00
R2061:Scn5a	UTSW	9	119485651	missense	probably damaging	0.98
R2083:Scn5a	UTSW	9	119492123	missense	probably benign	0.45
R2180:Scn5a	UTSW	9	119516051	missense	probably benign
R2216:Scn5a	UTSW	9	119485612	missense	probably benign	0.37
R2216:Scn5a	UTSW	9	119513085	missense	probably benign
R2320:Scn5a	UTSW	9	119529956	critical splice donor site	probably null
R2377:Scn5a	UTSW	9	119539727	missense	probably damaging	1.00
R2510:Scn5a	UTSW	9	119533685	missense	probably benign	0.05
R3113:Scn5a	UTSW	9	119485672	missense	probably damaging	1.00
R3769:Scn5a	UTSW	9	119552076	critical splice acceptor site	probably benign
R4133:Scn5a	UTSW	9	119486372	missense	probably damaging	1.00
R4164:Scn5a	UTSW	9	119495778	missense	probably damaging	1.00
R4447:Scn5a	UTSW	9	119550627	missense	probably damaging	1.00
R4635:Scn5a	UTSW	9	119528985	missense	possibly damaging	0.47
R4734:Scn5a	UTSW	9	119539538	missense	probably damaging	0.98
R4829:Scn5a	UTSW	9	119534707	missense	probably benign	0.00
R4867:Scn5a	UTSW	9	119550671	nonsense	probably null
R5055:Scn5a	UTSW	9	119522566	missense	probably damaging	1.00
R5229:Scn5a	UTSW	9	119535976	missense	probably damaging	1.00
R5344:Scn5a	UTSW	9	119534007	missense	probably benign	0.25
R5424:Scn5a	UTSW	9	119501734	missense	probably damaging	1.00
R5517:Scn5a	UTSW	9	119495713	missense	probably damaging	1.00
R5526:Scn5a	UTSW	9	119521171	missense	probably damaging	1.00
R5560:Scn5a	UTSW	9	119560286	missense	probably damaging	1.00
R5719:Scn5a	UTSW	9	119530052	missense	possibly damaging	0.91
R5726:Scn5a	UTSW	9	119533847	missense	probably damaging	1.00
R5800:Scn5a	UTSW	9	119501666	missense	probably damaging	1.00
R5826:Scn5a	UTSW	9	119521333	missense	probably damaging	1.00
R6046:Scn5a	UTSW	9	119562374	missense	probably damaging	1.00
R6101:Scn5a	UTSW	9	119522650	missense	probably damaging	0.98
R6162:Scn5a	UTSW	9	119522555	missense	probably damaging	0.98
R6375:Scn5a	UTSW	9	119543356	missense	probably damaging	1.00
R6378:Scn5a	UTSW	9	119486036	missense	probably damaging	1.00
R6464:Scn5a	UTSW	9	119534580	missense	probably damaging	1.00
R6794:Scn5a	UTSW	9	119535889	missense	probably damaging	0.98
R6799:Scn5a	UTSW	9	119495622	missense	possibly damaging	0.62
R6850:Scn5a	UTSW	9	119501749	missense	possibly damaging	0.92
R6858:Scn5a	UTSW	9	119492090	missense	probably benign	0.11
R6861:Scn5a	UTSW	9	119530023	missense	probably damaging	1.00
R6875:Scn5a	UTSW	9	119486644	missense	probably damaging	1.00
R6989:Scn5a	UTSW	9	119486329	missense	probably damaging	1.00
R7009:Scn5a	UTSW	9	119485930	missense	probably damaging	1.00
R7064:Scn5a	UTSW	9	119489911	missense	probably damaging	0.99
R7145:Scn5a	UTSW	9	119486371	missense	probably damaging	1.00
R7212:Scn5a	UTSW	9	119543385	missense	possibly damaging	0.94
R7238:Scn5a	UTSW	9	119491544	missense	possibly damaging	0.73
R7266:Scn5a	UTSW	9	119562560	missense	probably benign	0.37
R7348:Scn5a	UTSW	9	119535833	missense	probably benign	0.00
R7399:Scn5a	UTSW	9	119486530	missense	probably damaging	1.00
R7453:Scn5a	UTSW	9	119522590	missense	possibly damaging	0.82
R7495:Scn5a	UTSW	9	119543134	missense	probably damaging	0.99
R7681:Scn5a	UTSW	9	119529977	missense	probably benign	0.01
R7729:Scn5a	UTSW	9	119495540	missense	probably damaging	1.00
R7791:Scn5a	UTSW	9	119543336	missense	possibly damaging	0.47
R7794:Scn5a	UTSW	9	119529087	missense	probably damaging	0.99
R7873:Scn5a	UTSW	9	119498127	missense	probably damaging	1.00
R7951:Scn5a	UTSW	9	119529079	missense	probably damaging	1.00
R8154:Scn5a	UTSW	9	119562545	missense	possibly damaging	0.48
R8306:Scn5a	UTSW	9	119521291	missense	probably damaging	1.00
R8329:Scn5a	UTSW	9	119535964	missense	probably damaging	0.96
R8390:Scn5a	UTSW	9	119539538	missense	possibly damaging	0.59
R8536:Scn5a	UTSW	9	119539745	missense	probably damaging	1.00
R8922:Scn5a	UTSW	9	119534700	missense	probably benign
R9000:Scn5a	UTSW	9	119492105	missense	possibly damaging	0.95
R9015:Scn5a	UTSW	9	119552076	critical splice acceptor site	probably benign
R9272:Scn5a	UTSW	9	119486651	missense	probably damaging	1.00
R9394:Scn5a	UTSW	9	119495616	missense	probably damaging	1.00
R9448:Scn5a	UTSW	9	119552061	missense	probably damaging	0.99
R9511:Scn5a	UTSW	9	119522545	missense	probably benign	0.00
R9563:Scn5a	UTSW	9	119486737	missense	probably damaging	1.00
R9593:Scn5a	UTSW	9	119486773	missense	probably damaging	1.00
X0023:Scn5a	UTSW	9	119517769	missense	probably damaging	1.00
X0065:Scn5a	UTSW	9	119485669	missense	probably damaging	1.00
Z1177:Scn5a	UTSW	9	119522518	missense	probably damaging	1.00
Z1177:Scn5a	UTSW	9	119533931	missense	probably benign	0.04

Predicted Primers

PCR Primer
(F):5'- ACGGCGTGATTTATGTCTGTATCCC -3'
(R):5'- AGATGGCAAACTTCCTGTTACCTCG -3'

Sequencing Primer
(F):5'- CGTGATTTATGTCTGTATCCCAGAAC -3'
(R):5'- AGCAGCTTCCGTAGGTTCAC -3'

Posted On

2014-05-09