Mutagenetix > Incidental Mutation

Incidental Mutation 'R5800:Scn5a'

447354

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

043389-MU

Accession Numbers

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

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R5800 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

119483408-119579016 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 119501666 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Tyrosine to Histidine at position 1269 (Y1269H)

Ref Sequence

ENSEMBL: ENSMUSP00000066228 (fasta)

Gene Model

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

AlphaFold

Q9JJV9

Predicted Effect

probably damaging
Transcript: ENSMUST00000065196
AA Change: Y1269H

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000066228
Gene: ENSMUSG00000032511
AA Change: Y1269H

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: Y1269H

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000112838
Gene: ENSMUSG00000032511
AA Change: Y1269H

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: Y1268H

PolyPhen 2 Score 0.978 (Sensitivity: 0.76; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000113272
Gene: ENSMUSG00000032511
AA Change: Y1268H

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

Meta Mutation Damage Score

0.9734

Coding Region Coverage

1x: 99.3%
3x: 98.7%
10x: 97.3%
20x: 95.4%

Validation Efficiency

96% (50/52)

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: 50 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1520401A03Rik	G	A	17: 23,717,992	P72S	probably damaging	Het
4932438A13Rik	A	G	3: 37,052,443	D4974G	probably damaging	Het
Abca12	A	T	1: 71,321,432	V540D	possibly damaging	Het
Adamts8	A	T	9: 30,954,482	D442V	probably damaging	Het
Casp4	G	A	9: 5,308,915		probably null	Het
Cfap45	T	A	1: 172,538,600	V30E	probably damaging	Het
Col6a4	A	G	9: 106,080,275	F117L	probably damaging	Het
Dnah7c	A	T	1: 46,647,015	T1810S	probably benign	Het
Drosha	C	T	15: 12,865,067	T627M	probably damaging	Het
Drosha	C	A	15: 12,902,647	A1001D	probably damaging	Het
Efhc1	G	A	1: 20,978,781	V473I	probably benign	Het
Ephx2	T	C	14: 66,107,302	K191R	probably benign	Het
Ero1lb	T	A	13: 12,602,301		probably null	Het
Esyt2	A	T	12: 116,370,188	D837V	possibly damaging	Het
Fip1l1	T	A	5: 74,546,081	D126E	possibly damaging	Het
Fyttd1	C	T	16: 32,891,288	R86C	probably damaging	Het
Gm12888	T	A	4: 121,319,428	T59S	probably damaging	Het
Gm34653	T	C	2: 34,838,642	F151S	possibly damaging	Het
Gm7353	A	T	7: 3,110,168		noncoding transcript	Het
Gpr153	C	T	4: 152,280,077	Q197*	probably null	Het
H2-T23	G	T	17: 36,031,604		probably benign	Het
Ighv1-16	T	A	12: 114,665,911	R85S	probably benign	Het
Ipcef1	T	A	10: 6,890,569	D376V	probably damaging	Het
Kdm1a	T	A	4: 136,573,070		probably null	Het
Klk1b27	A	T	7: 44,055,664	Q85L	probably benign	Het
Krt39	A	T	11: 99,521,145	D38E	probably benign	Het
L1td1	T	C	4: 98,733,762	L187P	possibly damaging	Het
Lrrc8b	C	T	5: 105,481,342	S518L	probably benign	Het
Lyg1	C	T	1: 37,946,953	D176N	probably damaging	Het
Mctp1	A	G	13: 76,688,559	N82D	probably damaging	Het
Muc6	T	C	7: 141,640,423		probably benign	Het
Nynrin	T	C	14: 55,870,631	L1065P	probably damaging	Het
Olfr1474	T	C	19: 13,471,896	S309P	probably benign	Het
Pcdh7	T	A	5: 57,722,225	S1041T	probably damaging	Het
Pkd1l1	T	A	11: 8,861,302	M1518L	probably benign	Het
Prl8a6	G	T	13: 27,435,470	Q90K	probably benign	Het
Ptcd1	T	A	5: 145,159,665	D206V	probably damaging	Het
Rap1gap	C	A	4: 137,720,377	D478E	probably benign	Het
Sdc2	A	T	15: 33,028,144	H136L	probably benign	Het
Senp6	A	T	9: 80,126,433	I120F	probably damaging	Het
Shisa5	G	A	9: 109,056,094		probably null	Het
Slc19a1	A	G	10: 77,042,269	S213G	probably null	Het
Smim8	TTTAATGAAGAGCT	TT	4: 34,771,261		probably benign	Het
Tbc1d20	T	A	2: 152,308,325		probably null	Het
Tll2	T	C	19: 41,104,934	H481R	probably benign	Het
Tmc7	A	G	7: 118,539,440	V692A	probably benign	Het
Tmem234	T	C	4: 129,607,131		probably null	Het
Vmn1r237	C	G	17: 21,314,807	T264S	probably benign	Het
Vmn2r98	A	T	17: 19,065,998	T253S	probably benign	Het
Zfyve27	T	C	19: 42,182,663	Y191H	probably damaging	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
R1657:Scn5a	UTSW	9	119562380	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
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'- AGGTCTAGGCTTCAGTCTCCTG -3'
(R):5'- ATGTACCTCCTTCACGGGTG -3'

Sequencing Primer
(F):5'- AGGCTTCAGTCTCCTGGTTTC -3'
(R):5'- CAGCAGCTGGGAATTGTGC -3'

Posted On

2016-12-15