Mutagenetix > Incidental Mutation

Incidental Mutation 'R6375:Scn5a'

514922

Institutional Source

Beutler Lab

Gene Symbol

Scn5a

Ensembl Gene

ENSMUSG00000032511

Gene Name

sodium channel, voltage-gated, type V, alpha

Synonyms

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

MMRRC Submission

044525-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R6375 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

119312474-119408082 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 119372422 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Leucine to Glutamine at position 224 (L224Q)

Ref Sequence

ENSEMBL: ENSMUSP00000112838 (fasta)

Gene Model

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

AlphaFold

Q9JJV9

Predicted Effect

probably benign
Transcript: ENSMUST00000065196

SMART Domains

Protein: ENSMUSP00000066228
Gene: ENSMUSG00000032511

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: L224Q

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

SMART Domains

Protein: ENSMUSP00000112838
Gene: ENSMUSG00000032511
AA Change: L224Q

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 benign
Transcript: ENSMUST00000120420

SMART Domains

Protein: ENSMUSP00000113272
Gene: ENSMUSG00000032511

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

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.2%
20x: 97.2%

Validation Efficiency

100% (45/45)

MGI Phenotype

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: 46 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abca3	T	A	17: 24,606,536 (GRCm39)	I797N	possibly damaging	Het
Actbl2	A	G	13: 111,392,478 (GRCm39)	E271G	probably damaging	Het
Aplp2	T	C	9: 31,069,084 (GRCm39)	N526D	probably benign	Het
Cacna1e	A	C	1: 154,355,051 (GRCm39)	N389K	probably damaging	Het
Ccdc18	T	C	5: 108,322,820 (GRCm39)	I640T	possibly damaging	Het
Ccdc39	T	A	3: 33,868,516 (GRCm39)	T857S	probably benign	Het
Ccser1	T	A	6: 61,288,152 (GRCm39)	L105*	probably null	Het
Efhc1	T	A	1: 21,043,164 (GRCm39)	M361K	probably benign	Het
Eml5	T	C	12: 98,765,127 (GRCm39)			Het
Fgfr2	C	A	7: 129,769,475 (GRCm39)	L637F	probably damaging	Het
Fmo9	A	G	1: 166,492,164 (GRCm39)		probably null	Het
Gm4302	A	G	10: 100,177,258 (GRCm39)	T181A	probably benign	Het
Gpat2	G	C	2: 127,273,838 (GRCm39)	G294R	possibly damaging	Het
Hoxb4	A	G	11: 96,211,153 (GRCm39)	*251W	probably null	Het
Il1r1	T	A	1: 40,334,050 (GRCm39)	Y207N	probably damaging	Het
Kcnc2	C	T	10: 112,299,094 (GRCm39)	T622M	possibly damaging	Het
Kcnk9	C	T	15: 72,418,092 (GRCm39)	A13T	probably benign	Het
Kdm4c	C	T	4: 74,248,952 (GRCm39)	P69S	probably damaging	Het
Kmt2e	T	C	5: 23,704,517 (GRCm39)	S1237P	probably benign	Het
Lrrc37a	G	A	11: 103,391,915 (GRCm39)	T1170I	probably benign	Het
Lyn	T	A	4: 3,745,527 (GRCm39)	F109I	probably damaging	Het
Lynx1	T	C	15: 74,623,168 (GRCm39)	Y88C	probably damaging	Het
Mon1b	T	A	8: 114,364,709 (GRCm39)	I162N	probably damaging	Het
Muc4	A	G	16: 32,555,061 (GRCm39)		probably benign	Het
Nbn	T	A	4: 15,979,327 (GRCm39)	F437L	probably benign	Het
Neil3	T	C	8: 54,040,311 (GRCm39)	K564E	possibly damaging	Het
Nfe2l1	A	T	11: 96,710,877 (GRCm39)	S293T	probably damaging	Het
Or10al5	T	A	17: 38,062,990 (GRCm39)	S82T	probably benign	Het
Or14c39	C	T	7: 86,344,267 (GRCm39)	A201V	probably benign	Het
Or2ag2	C	A	7: 106,485,221 (GRCm39)	A268S	probably benign	Het
Or51g2	T	C	7: 102,622,960 (GRCm39)	T80A	probably damaging	Het
Pcdhb22	A	T	18: 37,651,357 (GRCm39)		probably benign	Het
Pcdhgb6	A	G	18: 37,875,678 (GRCm39)	N129D	probably damaging	Het
Pias2	C	T	18: 77,240,366 (GRCm39)	T574M	possibly damaging	Het
Plec	G	A	15: 76,061,840 (GRCm39)	T2564I	probably damaging	Het
Qrich2	A	G	11: 116,349,054 (GRCm39)		probably benign	Het
Scgb1b12	T	A	7: 32,033,884 (GRCm39)	V48E	probably damaging	Het
Snx3	T	A	10: 42,410,727 (GRCm39)	Y132*	probably null	Het
Stk39	T	A	2: 68,222,582 (GRCm39)	I161F	probably benign	Het
Tcaf2	A	C	6: 42,603,112 (GRCm39)	L816R	probably damaging	Het
Thap4	C	A	1: 93,652,878 (GRCm39)		probably null	Het
Tmc5	T	A	7: 118,256,037 (GRCm39)	V704E	probably damaging	Het
Tmem39a	A	G	16: 38,405,599 (GRCm39)	T59A	probably benign	Het
Tshz2	A	G	2: 169,727,939 (GRCm39)	N376S	probably damaging	Het
Vmn1r60	T	C	7: 5,548,017 (GRCm39)	N28D	probably damaging	Het
Zfp637	C	T	6: 117,822,285 (GRCm39)	R138W	probably damaging	Het

Other mutations in Scn5a

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00336:Scn5a	APN	9	119,315,290 (GRCm39)	missense	probably damaging	1.00
IGL00480:Scn5a	APN	9	119,346,604 (GRCm39)	missense	possibly damaging	0.73
IGL00542:Scn5a	APN	9	119,321,192 (GRCm39)	missense	probably damaging	1.00
IGL00852:Scn5a	APN	9	119,366,748 (GRCm39)	missense	probably benign	0.26
IGL00895:Scn5a	APN	9	119,342,170 (GRCm39)	splice site	probably null
IGL00905:Scn5a	APN	9	119,365,567 (GRCm39)	missense	probably damaging	1.00
IGL01347:Scn5a	APN	9	119,391,507 (GRCm39)	nonsense	probably null
IGL01396:Scn5a	APN	9	119,363,770 (GRCm39)	missense	probably damaging	0.98
IGL01402:Scn5a	APN	9	119,315,536 (GRCm39)	missense	probably damaging	1.00
IGL01404:Scn5a	APN	9	119,315,536 (GRCm39)	missense	probably damaging	1.00
IGL01487:Scn5a	APN	9	119,391,689 (GRCm39)	start codon destroyed	probably null	0.90
IGL01612:Scn5a	APN	9	119,315,091 (GRCm39)	missense	possibly damaging	0.86
IGL02134:Scn5a	APN	9	119,314,958 (GRCm39)	missense	probably damaging	0.98
IGL02434:Scn5a	APN	9	119,362,859 (GRCm39)	missense	possibly damaging	0.83
IGL02698:Scn5a	APN	9	119,350,163 (GRCm39)	missense	probably damaging	1.00
IGL02717:Scn5a	APN	9	119,358,076 (GRCm39)	missense	probably benign	0.12
IGL02746:Scn5a	APN	9	119,379,703 (GRCm39)	missense	probably damaging	1.00
IGL02951:Scn5a	APN	9	119,324,751 (GRCm39)	missense	probably damaging	1.00
IGL03155:Scn5a	APN	9	119,341,248 (GRCm39)	missense	possibly damaging	0.74
IGL03188:Scn5a	APN	9	119,351,632 (GRCm39)	missense	probably damaging	1.00
IGL03268:Scn5a	APN	9	119,350,297 (GRCm39)	missense	probably damaging	1.00
IGL03287:Scn5a	APN	9	119,318,844 (GRCm39)	missense	probably damaging	1.00
IGL03328:Scn5a	APN	9	119,366,702 (GRCm39)	missense	probably benign	0.12
PIT4142001:Scn5a	UTSW	9	119,315,324 (GRCm39)	missense	probably damaging	1.00
PIT4520001:Scn5a	UTSW	9	119,363,636 (GRCm39)	missense	possibly damaging	0.56
R0026:Scn5a	UTSW	9	119,351,632 (GRCm39)	missense	probably damaging	1.00
R0044:Scn5a	UTSW	9	119,321,113 (GRCm39)	critical splice donor site	probably null
R0044:Scn5a	UTSW	9	119,321,113 (GRCm39)	critical splice donor site	probably null
R0267:Scn5a	UTSW	9	119,372,201 (GRCm39)	missense	probably damaging	0.98
R0313:Scn5a	UTSW	9	119,363,637 (GRCm39)	missense	probably damaging	1.00
R0360:Scn5a	UTSW	9	119,351,665 (GRCm39)	missense	probably damaging	0.99
R0364:Scn5a	UTSW	9	119,351,665 (GRCm39)	missense	probably damaging	0.99
R0369:Scn5a	UTSW	9	119,362,838 (GRCm39)	missense	probably damaging	0.99
R0512:Scn5a	UTSW	9	119,379,724 (GRCm39)	missense	probably damaging	1.00
R0681:Scn5a	UTSW	9	119,368,706 (GRCm39)	missense	probably damaging	0.96
R1163:Scn5a	UTSW	9	119,362,993 (GRCm39)	missense	probably damaging	1.00
R1469:Scn5a	UTSW	9	119,362,727 (GRCm39)	critical splice donor site	probably null
R1469:Scn5a	UTSW	9	119,362,727 (GRCm39)	critical splice donor site	probably null
R1470:Scn5a	UTSW	9	119,365,541 (GRCm39)	missense	possibly damaging	0.82
R1470:Scn5a	UTSW	9	119,365,541 (GRCm39)	missense	possibly damaging	0.82
R1530:Scn5a	UTSW	9	119,324,628 (GRCm39)	missense	probably damaging	1.00
R1532:Scn5a	UTSW	9	119,362,913 (GRCm39)	missense	probably damaging	1.00
R1544:Scn5a	UTSW	9	119,315,699 (GRCm39)	missense	probably damaging	1.00
R1588:Scn5a	UTSW	9	119,350,367 (GRCm39)	missense	probably damaging	1.00
R1597:Scn5a	UTSW	9	119,391,563 (GRCm39)	missense	probably damaging	0.99
R1607:Scn5a	UTSW	9	119,315,158 (GRCm39)	missense	probably damaging	1.00
R1657:Scn5a	UTSW	9	119,391,446 (GRCm39)	missense	probably damaging	1.00
R1664:Scn5a	UTSW	9	119,350,243 (GRCm39)	missense	possibly damaging	0.84
R1785:Scn5a	UTSW	9	119,350,195 (GRCm39)	missense	probably damaging	1.00
R1925:Scn5a	UTSW	9	119,358,085 (GRCm39)	missense	probably benign
R1956:Scn5a	UTSW	9	119,346,479 (GRCm39)	missense	possibly damaging	0.82
R2006:Scn5a	UTSW	9	119,365,546 (GRCm39)	missense	probably damaging	1.00
R2061:Scn5a	UTSW	9	119,314,717 (GRCm39)	missense	probably damaging	0.98
R2083:Scn5a	UTSW	9	119,321,189 (GRCm39)	missense	probably benign	0.45
R2180:Scn5a	UTSW	9	119,345,117 (GRCm39)	missense	probably benign
R2216:Scn5a	UTSW	9	119,342,151 (GRCm39)	missense	probably benign
R2216:Scn5a	UTSW	9	119,314,678 (GRCm39)	missense	probably benign	0.37
R2320:Scn5a	UTSW	9	119,359,022 (GRCm39)	critical splice donor site	probably null
R2377:Scn5a	UTSW	9	119,368,793 (GRCm39)	missense	probably damaging	1.00
R2510:Scn5a	UTSW	9	119,362,751 (GRCm39)	missense	probably benign	0.05
R3113:Scn5a	UTSW	9	119,314,738 (GRCm39)	missense	probably damaging	1.00
R3769:Scn5a	UTSW	9	119,381,142 (GRCm39)	critical splice acceptor site	probably benign
R4133:Scn5a	UTSW	9	119,315,438 (GRCm39)	missense	probably damaging	1.00
R4164:Scn5a	UTSW	9	119,324,844 (GRCm39)	missense	probably damaging	1.00
R4447:Scn5a	UTSW	9	119,379,693 (GRCm39)	missense	probably damaging	1.00
R4635:Scn5a	UTSW	9	119,358,051 (GRCm39)	missense	possibly damaging	0.47
R4734:Scn5a	UTSW	9	119,368,604 (GRCm39)	missense	probably damaging	0.98
R4829:Scn5a	UTSW	9	119,363,773 (GRCm39)	missense	probably benign	0.00
R4867:Scn5a	UTSW	9	119,379,737 (GRCm39)	nonsense	probably null
R5055:Scn5a	UTSW	9	119,351,632 (GRCm39)	missense	probably damaging	1.00
R5229:Scn5a	UTSW	9	119,365,042 (GRCm39)	missense	probably damaging	1.00
R5344:Scn5a	UTSW	9	119,363,073 (GRCm39)	missense	probably benign	0.25
R5424:Scn5a	UTSW	9	119,330,800 (GRCm39)	missense	probably damaging	1.00
R5517:Scn5a	UTSW	9	119,324,779 (GRCm39)	missense	probably damaging	1.00
R5526:Scn5a	UTSW	9	119,350,237 (GRCm39)	missense	probably damaging	1.00
R5560:Scn5a	UTSW	9	119,389,352 (GRCm39)	missense	probably damaging	1.00
R5719:Scn5a	UTSW	9	119,359,118 (GRCm39)	missense	possibly damaging	0.91
R5726:Scn5a	UTSW	9	119,362,913 (GRCm39)	missense	probably damaging	1.00
R5800:Scn5a	UTSW	9	119,330,732 (GRCm39)	missense	probably damaging	1.00
R5826:Scn5a	UTSW	9	119,350,399 (GRCm39)	missense	probably damaging	1.00
R6046:Scn5a	UTSW	9	119,391,440 (GRCm39)	missense	probably damaging	1.00
R6101:Scn5a	UTSW	9	119,351,716 (GRCm39)	missense	probably damaging	0.98
R6162:Scn5a	UTSW	9	119,351,621 (GRCm39)	missense	probably damaging	0.98
R6378:Scn5a	UTSW	9	119,315,102 (GRCm39)	missense	probably damaging	1.00
R6464:Scn5a	UTSW	9	119,363,646 (GRCm39)	missense	probably damaging	1.00
R6794:Scn5a	UTSW	9	119,364,955 (GRCm39)	missense	probably damaging	0.98
R6799:Scn5a	UTSW	9	119,324,688 (GRCm39)	missense	possibly damaging	0.62
R6850:Scn5a	UTSW	9	119,330,815 (GRCm39)	missense	possibly damaging	0.92
R6858:Scn5a	UTSW	9	119,321,156 (GRCm39)	missense	probably benign	0.11
R6861:Scn5a	UTSW	9	119,359,089 (GRCm39)	missense	probably damaging	1.00
R6875:Scn5a	UTSW	9	119,315,710 (GRCm39)	missense	probably damaging	1.00
R6989:Scn5a	UTSW	9	119,315,395 (GRCm39)	missense	probably damaging	1.00
R7009:Scn5a	UTSW	9	119,314,996 (GRCm39)	missense	probably damaging	1.00
R7064:Scn5a	UTSW	9	119,318,977 (GRCm39)	missense	probably damaging	0.99
R7145:Scn5a	UTSW	9	119,315,437 (GRCm39)	missense	probably damaging	1.00
R7212:Scn5a	UTSW	9	119,372,451 (GRCm39)	missense	possibly damaging	0.94
R7238:Scn5a	UTSW	9	119,320,610 (GRCm39)	missense	possibly damaging	0.73
R7266:Scn5a	UTSW	9	119,391,626 (GRCm39)	missense	probably benign	0.37
R7348:Scn5a	UTSW	9	119,364,899 (GRCm39)	missense	probably benign	0.00
R7399:Scn5a	UTSW	9	119,315,596 (GRCm39)	missense	probably damaging	1.00
R7453:Scn5a	UTSW	9	119,351,656 (GRCm39)	missense	possibly damaging	0.82
R7495:Scn5a	UTSW	9	119,372,200 (GRCm39)	missense	probably damaging	0.99
R7681:Scn5a	UTSW	9	119,359,043 (GRCm39)	missense	probably benign	0.01
R7729:Scn5a	UTSW	9	119,324,606 (GRCm39)	missense	probably damaging	1.00
R7791:Scn5a	UTSW	9	119,372,402 (GRCm39)	missense	possibly damaging	0.47
R7794:Scn5a	UTSW	9	119,358,153 (GRCm39)	missense	probably damaging	0.99
R7873:Scn5a	UTSW	9	119,327,193 (GRCm39)	missense	probably damaging	1.00
R7951:Scn5a	UTSW	9	119,358,145 (GRCm39)	missense	probably damaging	1.00
R8154:Scn5a	UTSW	9	119,391,611 (GRCm39)	missense	possibly damaging	0.48
R8306:Scn5a	UTSW	9	119,350,357 (GRCm39)	missense	probably damaging	1.00
R8329:Scn5a	UTSW	9	119,365,030 (GRCm39)	missense	probably damaging	0.96
R8390:Scn5a	UTSW	9	119,368,604 (GRCm39)	missense	possibly damaging	0.59
R8536:Scn5a	UTSW	9	119,368,811 (GRCm39)	missense	probably damaging	1.00
R8922:Scn5a	UTSW	9	119,363,766 (GRCm39)	missense	probably benign
R9000:Scn5a	UTSW	9	119,321,171 (GRCm39)	missense	possibly damaging	0.95
R9015:Scn5a	UTSW	9	119,381,142 (GRCm39)	critical splice acceptor site	probably benign
R9272:Scn5a	UTSW	9	119,315,717 (GRCm39)	missense	probably damaging	1.00
R9394:Scn5a	UTSW	9	119,324,682 (GRCm39)	missense	probably damaging	1.00
R9448:Scn5a	UTSW	9	119,381,127 (GRCm39)	missense	probably damaging	0.99
R9511:Scn5a	UTSW	9	119,351,611 (GRCm39)	missense	probably benign	0.00
R9563:Scn5a	UTSW	9	119,315,803 (GRCm39)	missense	probably damaging	1.00
R9593:Scn5a	UTSW	9	119,315,839 (GRCm39)	missense	probably damaging	1.00
X0023:Scn5a	UTSW	9	119,346,835 (GRCm39)	missense	probably damaging	1.00
X0065:Scn5a	UTSW	9	119,314,735 (GRCm39)	missense	probably damaging	1.00
Z1177:Scn5a	UTSW	9	119,362,997 (GRCm39)	missense	probably benign	0.04
Z1177:Scn5a	UTSW	9	119,351,584 (GRCm39)	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- TGCCCAGGTCCACAAATTCAG -3'
(R):5'- ACGGCTAGGCTGAGATCTTG -3'

Sequencing Primer
(F):5'- CAGTTGTGTATCTGTAACAAGGGAG -3'
(R):5'- GAGGGCCCAAGTCTACCAC -3'

Posted On

2018-05-04