Mutagenetix > Incidental Mutation

Incidental Mutation 'R0026:Scn5a'

189180

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

038321-MU

Accession Numbers

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

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R0026 (G1)

Quality Score

Status

Validated

Chromosome

Chromosomal Location

119483408-119579016 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 119522566 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Isoleucine to Threonine at position 783 (I783T)

Ref Sequence

ENSEMBL: ENSMUSP00000112838 (fasta)

Gene Model

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

AlphaFold

Q9JJV9

Predicted Effect

probably damaging
Transcript: ENSMUST00000065196
AA Change: I783T

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

SMART Domains

Protein: ENSMUSP00000066228
Gene: ENSMUSG00000032511
AA Change: I783T

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: I783T

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

SMART Domains

Protein: ENSMUSP00000112838
Gene: ENSMUSG00000032511
AA Change: I783T

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: I783T

PolyPhen 2 Score 0.995 (Sensitivity: 0.68; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000113272
Gene: ENSMUSG00000032511
AA Change: I783T

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

0.8777

Coding Region Coverage

1x: 99.3%
3x: 98.9%
10x: 97.8%
20x: 96.3%

Validation Efficiency

93% (70/75)

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: 61 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1110002E22Rik	T	A	3: 138,066,805	I585N	possibly damaging	Het
4931408C20Rik	T	A	1: 26,683,369	D910V	probably benign	Het
A830005F24Rik	C	T	13: 48,514,372		probably benign	Het
Abca16	C	T	7: 120,477,923		probably benign	Het
Acot10	G	A	15: 20,666,236	L140F	probably benign	Het
Adam19	G	T	11: 46,136,259	C573F	probably damaging	Het
Aff3	A	G	1: 38,203,893	S948P	probably benign	Het
Anxa3	T	A	5: 96,838,401	Y300N	probably benign	Het
BC016579	T	C	16: 45,640,367	T113A	probably benign	Het
Bmpr1b	A	G	3: 141,870,733	L113P	probably benign	Het
Casq1	T	C	1: 172,219,400		probably benign	Het
Cdc16	T	A	8: 13,759,130		probably null	Het
Cep135	C	T	5: 76,606,734	R353*	probably null	Het
Cma1	A	T	14: 55,942,164	C188S	probably damaging	Het
Csf3r	A	G	4: 126,031,884	T151A	probably benign	Het
Cyp4b1	C	T	4: 115,647,521	G56D	possibly damaging	Het
Dbn1	T	C	13: 55,477,784	E275G	probably damaging	Het
Dlgap2	C	T	8: 14,727,363	Q203*	probably null	Het
Ephb3	A	G	16: 21,214,917	D251G	probably damaging	Het
Fancd2os	G	T	6: 113,597,691	T118N	probably damaging	Het
Gm10801	T	C	2: 98,663,909		probably benign	Het
Got1l1	C	T	8: 27,200,248	V132I	probably benign	Het
H2-M9	T	C	17: 36,641,527		probably benign	Het
Ibtk	A	G	9: 85,690,303	V1278A	probably benign	Het
Kctd3	T	C	1: 188,976,621	T519A	probably damaging	Het
Lgsn	T	A	1: 31,203,443	V202D	probably damaging	Het
Madd	A	G	2: 91,175,708	F381L	possibly damaging	Het
Map1s	G	A	8: 70,914,638	G729D	probably damaging	Het
Mlycd	A	G	8: 119,410,435	I465V	probably benign	Het
Mrgprb1	T	C	7: 48,447,204	R108G	possibly damaging	Het
Mrgprx2	T	A	7: 48,482,023	H106L	possibly damaging	Het
Ncor1	T	C	11: 62,438,429	Y6C	probably damaging	Het
Nfkb1	T	C	3: 135,591,573	D773G	probably damaging	Het
Nxnl1	A	G	8: 71,566,573	S3P	probably damaging	Het
Olfr109	T	A	17: 37,466,803	V199D	probably damaging	Het
Olfr921	G	A	9: 38,775,596	V114I	probably benign	Het
Otud7a	T	C	7: 63,735,801	F338L	probably benign	Het
Pdcl3	T	A	1: 38,991,280	L14Q	probably damaging	Het
Pla2g7	T	A	17: 43,594,930		probably benign	Het
Prpf31	T	A	7: 3,639,668	N413K	probably benign	Het
Rapgef5	T	C	12: 117,689,161	S307P	probably benign	Het
Relt	C	A	7: 100,850,221	E164*	probably null	Het
Rnf185	T	C	11: 3,426,617	D86G	probably damaging	Het
Rrm2b	T	C	15: 37,953,741	E21G	probably benign	Het
Senp1	T	C	15: 98,076,668	R88G	probably damaging	Het
Skint5	A	T	4: 113,546,468		probably benign	Het
Slc35b1	T	C	11: 95,390,642	S294P	probably benign	Het
Slc5a2	T	A	7: 128,270,053	I335N	probably damaging	Het
Sstr1	T	A	12: 58,212,858	M89K	probably damaging	Het
Szt2	A	T	4: 118,384,772	S1612R	possibly damaging	Het
Taf1c	T	C	8: 119,604,236		probably null	Het
Taf1d	T	A	9: 15,308,648	S64R	probably damaging	Het
Tmem125	A	G	4: 118,542,073	S54P	possibly damaging	Het
Ttf1	T	A	2: 29,071,349	I583N	possibly damaging	Het
Uchl4	A	T	9: 64,235,371		probably null	Het
Unc5b	A	T	10: 60,774,592	I482N	possibly damaging	Het
Unc80	C	A	1: 66,521,584	Q824K	probably benign	Het
Utrn	T	C	10: 12,726,196		probably benign	Het
Vmn2r61	T	G	7: 42,275,474	I484R	possibly damaging	Het
Vps13b	T	C	15: 35,923,301	I3774T	possibly damaging	Het
Yipf1	T	A	4: 107,345,160	L240*	probably null	Het

Other mutations in Scn5a

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00336:Scn5a	APN	9	119,486,224 (GRCm38)	missense	probably damaging	1.00
IGL00480:Scn5a	APN	9	119,517,538 (GRCm38)	missense	possibly damaging	0.73
IGL00542:Scn5a	APN	9	119,492,126 (GRCm38)	missense	probably damaging	1.00
IGL00852:Scn5a	APN	9	119,537,682 (GRCm38)	missense	probably benign	0.26
IGL00895:Scn5a	APN	9	119,513,104 (GRCm38)	splice site	probably null
IGL00905:Scn5a	APN	9	119,536,501 (GRCm38)	missense	probably damaging	1.00
IGL01347:Scn5a	APN	9	119,562,441 (GRCm38)	nonsense	probably null
IGL01396:Scn5a	APN	9	119,534,704 (GRCm38)	missense	probably damaging	0.98
IGL01402:Scn5a	APN	9	119,486,470 (GRCm38)	missense	probably damaging	1.00
IGL01404:Scn5a	APN	9	119,486,470 (GRCm38)	missense	probably damaging	1.00
IGL01487:Scn5a	APN	9	119,562,623 (GRCm38)	start codon destroyed	probably null	0.90
IGL01612:Scn5a	APN	9	119,486,025 (GRCm38)	missense	possibly damaging	0.86
IGL02134:Scn5a	APN	9	119,485,892 (GRCm38)	missense	probably damaging	0.98
IGL02434:Scn5a	APN	9	119,533,793 (GRCm38)	missense	possibly damaging	0.83
IGL02698:Scn5a	APN	9	119,521,097 (GRCm38)	missense	probably damaging	1.00
IGL02717:Scn5a	APN	9	119,529,010 (GRCm38)	missense	probably benign	0.12
IGL02746:Scn5a	APN	9	119,550,637 (GRCm38)	missense	probably damaging	1.00
IGL02951:Scn5a	APN	9	119,495,685 (GRCm38)	missense	probably damaging	1.00
IGL03155:Scn5a	APN	9	119,512,182 (GRCm38)	missense	possibly damaging	0.74
IGL03188:Scn5a	APN	9	119,522,566 (GRCm38)	missense	probably damaging	1.00
IGL03268:Scn5a	APN	9	119,521,231 (GRCm38)	missense	probably damaging	1.00
IGL03287:Scn5a	APN	9	119,489,778 (GRCm38)	missense	probably damaging	1.00
IGL03328:Scn5a	APN	9	119,537,636 (GRCm38)	missense	probably benign	0.12
PIT4142001:Scn5a	UTSW	9	119,486,258 (GRCm38)	missense	probably damaging	1.00
PIT4520001:Scn5a	UTSW	9	119,534,570 (GRCm38)	missense	possibly damaging	0.56
R0044:Scn5a	UTSW	9	119,492,047 (GRCm38)	critical splice donor site	probably null
R0044:Scn5a	UTSW	9	119,492,047 (GRCm38)	critical splice donor site	probably null
R0267:Scn5a	UTSW	9	119,543,135 (GRCm38)	missense	probably damaging	0.98
R0313:Scn5a	UTSW	9	119,534,571 (GRCm38)	missense	probably damaging	1.00
R0360:Scn5a	UTSW	9	119,522,599 (GRCm38)	missense	probably damaging	0.99
R0364:Scn5a	UTSW	9	119,522,599 (GRCm38)	missense	probably damaging	0.99
R0369:Scn5a	UTSW	9	119,533,772 (GRCm38)	missense	probably damaging	0.99
R0512:Scn5a	UTSW	9	119,550,658 (GRCm38)	missense	probably damaging	1.00
R0681:Scn5a	UTSW	9	119,539,640 (GRCm38)	missense	probably damaging	0.96
R1163:Scn5a	UTSW	9	119,533,927 (GRCm38)	missense	probably damaging	1.00
R1469:Scn5a	UTSW	9	119,533,661 (GRCm38)	critical splice donor site	probably null
R1469:Scn5a	UTSW	9	119,533,661 (GRCm38)	critical splice donor site	probably null
R1470:Scn5a	UTSW	9	119,536,475 (GRCm38)	missense	possibly damaging	0.82
R1470:Scn5a	UTSW	9	119,536,475 (GRCm38)	missense	possibly damaging	0.82
R1530:Scn5a	UTSW	9	119,495,562 (GRCm38)	missense	probably damaging	1.00
R1532:Scn5a	UTSW	9	119,533,847 (GRCm38)	missense	probably damaging	1.00
R1544:Scn5a	UTSW	9	119,486,633 (GRCm38)	missense	probably damaging	1.00
R1588:Scn5a	UTSW	9	119,521,301 (GRCm38)	missense	probably damaging	1.00
R1597:Scn5a	UTSW	9	119,562,497 (GRCm38)	missense	probably damaging	0.99
R1607:Scn5a	UTSW	9	119,486,092 (GRCm38)	missense	probably damaging	1.00
R1657:Scn5a	UTSW	9	119,562,380 (GRCm38)	missense	probably damaging	1.00
R1664:Scn5a	UTSW	9	119,521,177 (GRCm38)	missense	possibly damaging	0.84
R1785:Scn5a	UTSW	9	119,521,129 (GRCm38)	missense	probably damaging	1.00
R1925:Scn5a	UTSW	9	119,529,019 (GRCm38)	missense	probably benign
R1956:Scn5a	UTSW	9	119,517,413 (GRCm38)	missense	possibly damaging	0.82
R2006:Scn5a	UTSW	9	119,536,480 (GRCm38)	missense	probably damaging	1.00
R2061:Scn5a	UTSW	9	119,485,651 (GRCm38)	missense	probably damaging	0.98
R2083:Scn5a	UTSW	9	119,492,123 (GRCm38)	missense	probably benign	0.45
R2180:Scn5a	UTSW	9	119,516,051 (GRCm38)	missense	probably benign
R2216:Scn5a	UTSW	9	119,513,085 (GRCm38)	missense	probably benign
R2216:Scn5a	UTSW	9	119,485,612 (GRCm38)	missense	probably benign	0.37
R2320:Scn5a	UTSW	9	119,529,956 (GRCm38)	critical splice donor site	probably null
R2377:Scn5a	UTSW	9	119,539,727 (GRCm38)	missense	probably damaging	1.00
R2510:Scn5a	UTSW	9	119,533,685 (GRCm38)	missense	probably benign	0.05
R3113:Scn5a	UTSW	9	119,485,672 (GRCm38)	missense	probably damaging	1.00
R3769:Scn5a	UTSW	9	119,552,076 (GRCm38)	critical splice acceptor site	probably benign
R4133:Scn5a	UTSW	9	119,486,372 (GRCm38)	missense	probably damaging	1.00
R4164:Scn5a	UTSW	9	119,495,778 (GRCm38)	missense	probably damaging	1.00
R4447:Scn5a	UTSW	9	119,550,627 (GRCm38)	missense	probably damaging	1.00
R4635:Scn5a	UTSW	9	119,528,985 (GRCm38)	missense	possibly damaging	0.47
R4734:Scn5a	UTSW	9	119,539,538 (GRCm38)	missense	probably damaging	0.98
R4829:Scn5a	UTSW	9	119,534,707 (GRCm38)	missense	probably benign	0.00
R4867:Scn5a	UTSW	9	119,550,671 (GRCm38)	nonsense	probably null
R5055:Scn5a	UTSW	9	119,522,566 (GRCm38)	missense	probably damaging	1.00
R5229:Scn5a	UTSW	9	119,535,976 (GRCm38)	missense	probably damaging	1.00
R5344:Scn5a	UTSW	9	119,534,007 (GRCm38)	missense	probably benign	0.25
R5424:Scn5a	UTSW	9	119,501,734 (GRCm38)	missense	probably damaging	1.00
R5517:Scn5a	UTSW	9	119,495,713 (GRCm38)	missense	probably damaging	1.00
R5526:Scn5a	UTSW	9	119,521,171 (GRCm38)	missense	probably damaging	1.00
R5560:Scn5a	UTSW	9	119,560,286 (GRCm38)	missense	probably damaging	1.00
R5719:Scn5a	UTSW	9	119,530,052 (GRCm38)	missense	possibly damaging	0.91
R5726:Scn5a	UTSW	9	119,533,847 (GRCm38)	missense	probably damaging	1.00
R5800:Scn5a	UTSW	9	119,501,666 (GRCm38)	missense	probably damaging	1.00
R5826:Scn5a	UTSW	9	119,521,333 (GRCm38)	missense	probably damaging	1.00
R6046:Scn5a	UTSW	9	119,562,374 (GRCm38)	missense	probably damaging	1.00
R6101:Scn5a	UTSW	9	119,522,650 (GRCm38)	missense	probably damaging	0.98
R6162:Scn5a	UTSW	9	119,522,555 (GRCm38)	missense	probably damaging	0.98
R6375:Scn5a	UTSW	9	119,543,356 (GRCm38)	missense	probably damaging	1.00
R6378:Scn5a	UTSW	9	119,486,036 (GRCm38)	missense	probably damaging	1.00
R6464:Scn5a	UTSW	9	119,534,580 (GRCm38)	missense	probably damaging	1.00
R6794:Scn5a	UTSW	9	119,535,889 (GRCm38)	missense	probably damaging	0.98
R6799:Scn5a	UTSW	9	119,495,622 (GRCm38)	missense	possibly damaging	0.62
R6850:Scn5a	UTSW	9	119,501,749 (GRCm38)	missense	possibly damaging	0.92
R6858:Scn5a	UTSW	9	119,492,090 (GRCm38)	missense	probably benign	0.11
R6861:Scn5a	UTSW	9	119,530,023 (GRCm38)	missense	probably damaging	1.00
R6875:Scn5a	UTSW	9	119,486,644 (GRCm38)	missense	probably damaging	1.00
R6989:Scn5a	UTSW	9	119,486,329 (GRCm38)	missense	probably damaging	1.00
R7009:Scn5a	UTSW	9	119,485,930 (GRCm38)	missense	probably damaging	1.00
R7064:Scn5a	UTSW	9	119,489,911 (GRCm38)	missense	probably damaging	0.99
R7145:Scn5a	UTSW	9	119,486,371 (GRCm38)	missense	probably damaging	1.00
R7212:Scn5a	UTSW	9	119,543,385 (GRCm38)	missense	possibly damaging	0.94
R7238:Scn5a	UTSW	9	119,491,544 (GRCm38)	missense	possibly damaging	0.73
R7266:Scn5a	UTSW	9	119,562,560 (GRCm38)	missense	probably benign	0.37
R7348:Scn5a	UTSW	9	119,535,833 (GRCm38)	missense	probably benign	0.00
R7399:Scn5a	UTSW	9	119,486,530 (GRCm38)	missense	probably damaging	1.00
R7453:Scn5a	UTSW	9	119,522,590 (GRCm38)	missense	possibly damaging	0.82
R7495:Scn5a	UTSW	9	119,543,134 (GRCm38)	missense	probably damaging	0.99
R7681:Scn5a	UTSW	9	119,529,977 (GRCm38)	missense	probably benign	0.01
R7729:Scn5a	UTSW	9	119,495,540 (GRCm38)	missense	probably damaging	1.00
R7791:Scn5a	UTSW	9	119,543,336 (GRCm38)	missense	possibly damaging	0.47
R7794:Scn5a	UTSW	9	119,529,087 (GRCm38)	missense	probably damaging	0.99
R7873:Scn5a	UTSW	9	119,498,127 (GRCm38)	missense	probably damaging	1.00
R7951:Scn5a	UTSW	9	119,529,079 (GRCm38)	missense	probably damaging	1.00
R8154:Scn5a	UTSW	9	119,562,545 (GRCm38)	missense	possibly damaging	0.48
R8306:Scn5a	UTSW	9	119,521,291 (GRCm38)	missense	probably damaging	1.00
R8329:Scn5a	UTSW	9	119,535,964 (GRCm38)	missense	probably damaging	0.96
R8390:Scn5a	UTSW	9	119,539,538 (GRCm38)	missense	possibly damaging	0.59
R8536:Scn5a	UTSW	9	119,539,745 (GRCm38)	missense	probably damaging	1.00
R8922:Scn5a	UTSW	9	119,534,700 (GRCm38)	missense	probably benign
R9000:Scn5a	UTSW	9	119,492,105 (GRCm38)	missense	possibly damaging	0.95
R9015:Scn5a	UTSW	9	119,552,076 (GRCm38)	critical splice acceptor site	probably benign
R9272:Scn5a	UTSW	9	119,486,651 (GRCm38)	missense	probably damaging	1.00
R9394:Scn5a	UTSW	9	119,495,616 (GRCm38)	missense	probably damaging	1.00
R9448:Scn5a	UTSW	9	119,552,061 (GRCm38)	missense	probably damaging	0.99
R9511:Scn5a	UTSW	9	119,522,545 (GRCm38)	missense	probably benign	0.00
R9563:Scn5a	UTSW	9	119,486,737 (GRCm38)	missense	probably damaging	1.00
R9593:Scn5a	UTSW	9	119,486,773 (GRCm38)	missense	probably damaging	1.00
X0023:Scn5a	UTSW	9	119,517,769 (GRCm38)	missense	probably damaging	1.00
X0065:Scn5a	UTSW	9	119,485,669 (GRCm38)	missense	probably damaging	1.00
Z1177:Scn5a	UTSW	9	119,533,931 (GRCm38)	missense	probably benign	0.04
Z1177:Scn5a	UTSW	9	119,522,518 (GRCm38)	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- TGCTGGGACTAAGGAGGTACATGAC -3'
(R):5'- TGTTTCTGAGTTGATGAGCCTGACC -3'

Sequencing Primer
(F):5'- CTTGACATCATCAGGATGTGACAG -3'
(R):5'- TTGATGAGCCTGACCAGTCAC -3'

Posted On

2014-05-13