Mutagenetix > Incidental Mutation

Incidental Mutation 'R5517:Scn5a'

431358

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

043076-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R5517 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

119312474-119408082 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to G at 119324779 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Isoleucine to Leucine at position 1350 (I1350L)

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: I1350L

PolyPhen 2 Score 0.986 (Sensitivity: 0.74; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000066228
Gene: ENSMUSG00000032511
AA Change: I1350L

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: I1350L

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

SMART Domains

Protein: ENSMUSP00000112838
Gene: ENSMUSG00000032511
AA Change: I1350L

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

possibly damaging
Transcript: ENSMUST00000120420
AA Change: I1349L

PolyPhen 2 Score 0.755 (Sensitivity: 0.85; Specificity: 0.92)

SMART Domains

Protein: ENSMUSP00000113272
Gene: ENSMUSG00000032511
AA Change: I1349L

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

0.7658

Coding Region Coverage

1x: 98.5%
3x: 97.4%
10x: 95.2%
20x: 90.5%

Validation Efficiency

99% (67/68)

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: 54 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abcf1	C	T	17: 36,269,233 (GRCm39)	R675K	possibly damaging	Het
Aire	A	T	10: 77,875,525 (GRCm39)	S282T	probably benign	Het
Ak9	A	G	10: 41,216,887 (GRCm39)	E283G	probably benign	Het
Akap9	T	A	5: 4,051,665 (GRCm39)	D1477E	possibly damaging	Het
Ap2a1	T	C	7: 44,556,405 (GRCm39)	D273G	possibly damaging	Het
Apob	T	C	12: 8,040,906 (GRCm39)	L664P	probably damaging	Het
Arhgap35	A	T	7: 16,297,414 (GRCm39)	F550L	probably damaging	Het
Armc2	T	C	10: 41,839,846 (GRCm39)	E373G	probably benign	Het
Atp8b2	C	A	3: 89,853,338 (GRCm39)	A726S	probably benign	Het
C030048H21Rik	T	A	2: 26,145,899 (GRCm39)	Q87L	probably damaging	Het
Cd244a	T	A	1: 171,405,542 (GRCm39)		probably benign	Het
Cdk10	T	A	8: 123,957,326 (GRCm39)		probably null	Het
Cenpe	C	A	3: 134,929,026 (GRCm39)	P310Q	probably damaging	Het
Chuk	T	A	19: 44,085,972 (GRCm39)		probably null	Het
Crebl2	T	C	6: 134,828,139 (GRCm39)	S104P	probably benign	Het
Ddo	A	G	10: 40,523,726 (GRCm39)	K239E	probably benign	Het
Defb5	A	G	8: 19,300,868 (GRCm39)		probably null	Het
Dhx35	T	A	2: 158,676,832 (GRCm39)	M422K	probably damaging	Het
Fchsd1	C	T	18: 38,092,926 (GRCm39)		probably benign	Het
Gatm	G	A	2: 122,426,024 (GRCm39)	T409I	probably damaging	Het
Gdpd1	A	T	11: 86,950,332 (GRCm39)	D80E	probably damaging	Het
Gspt1	C	A	16: 11,071,843 (GRCm39)	G7C	unknown	Het
Hells	G	A	19: 38,943,244 (GRCm39)	S516N	probably benign	Het
Ints1	A	G	5: 139,738,542 (GRCm39)	S2069P	possibly damaging	Het
Kank4	G	A	4: 98,663,118 (GRCm39)	T690M	probably damaging	Het
Kcnq4	T	C	4: 120,573,006 (GRCm39)	N265S	possibly damaging	Het
Kif5b	C	A	18: 6,220,954 (GRCm39)	A385S	probably benign	Het
Map2	T	C	1: 66,454,415 (GRCm39)	S1102P	probably benign	Het
Mcm7	A	G	5: 138,163,133 (GRCm39)	S340P	possibly damaging	Het
Mcrs1	C	T	15: 99,144,876 (GRCm39)	R246H	possibly damaging	Het
Myo16	T	A	8: 10,610,226 (GRCm39)	M1189K	probably benign	Het
Or4d2	A	T	11: 87,783,892 (GRCm39)	I286N	probably damaging	Het
Or4k52	G	T	2: 111,610,804 (GRCm39)	M46I	probably benign	Het
Or7g29	G	A	9: 19,287,063 (GRCm39)	T38I	probably damaging	Het
Otog	A	G	7: 45,923,995 (GRCm39)	N1118S	probably damaging	Het
Pakap	T	C	4: 57,855,987 (GRCm39)	Y439H	probably damaging	Het
Pcdhb7	G	T	18: 37,474,846 (GRCm39)		probably benign	Het
Picalm	C	T	7: 89,819,806 (GRCm39)	T189I	possibly damaging	Het
Ptx4	T	A	17: 25,343,760 (GRCm39)	S337T	possibly damaging	Het
Rad51ap2	C	T	12: 11,508,313 (GRCm39)	S745L	probably benign	Het
Rspry1	G	A	8: 95,363,388 (GRCm39)		probably null	Het
Sgk2	T	C	2: 162,839,755 (GRCm39)	L121P	probably damaging	Het
Slc17a1	A	T	13: 24,056,575 (GRCm39)		probably benign	Het
Slc6a12	A	G	6: 121,331,298 (GRCm39)	N183S	probably benign	Het
Smg9	C	A	7: 24,114,338 (GRCm39)		probably benign	Het
Spred1	G	A	2: 117,008,195 (GRCm39)	S367N	probably damaging	Het
Srpra	T	C	9: 35,122,646 (GRCm39)	V21A	probably benign	Het
Taar2	A	T	10: 23,816,627 (GRCm39)	I56F	possibly damaging	Het
Taf1a	T	G	1: 183,177,323 (GRCm39)	L67R	probably damaging	Het
Tbc1d10b	C	A	7: 126,797,779 (GRCm39)	R787S	possibly damaging	Het
Topbp1	T	A	9: 103,213,313 (GRCm39)	N1044K	probably benign	Het
Usp24	A	G	4: 106,232,871 (GRCm39)	T886A	probably benign	Het
Vmn2r26	A	G	6: 124,027,676 (GRCm39)	D472G	probably damaging	Het
Zyg11a	T	C	4: 108,061,943 (GRCm39)	N286S	possibly 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
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
R6375:Scn5a	UTSW	9	119,372,422 (GRCm39)	missense	probably damaging	1.00
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'- CCCCACGTTGTCAAAGTTG -3'
(R):5'- GAGCTCTAGCCTTCATGACTG -3'

Sequencing Primer
(F):5'- AAAGTTGACTTTCACCTTGGTCCAG -3'
(R):5'- TAGCCTTCATGACTGGAAGATCC -3'

Posted On

2016-10-05