Mutagenetix > Incidental Mutation

Incidental Mutation 'R6875:Scn5a'

536384

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

044971-MU

Accession Numbers

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

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R6875 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

119483408-119579016 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 119486644 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Leucine to Proline at position 1666 (L1666P)

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: L1666P

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

SMART Domains

Protein: ENSMUSP00000066228
Gene: ENSMUSG00000032511
AA Change: L1666P

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: L1666P

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

SMART Domains

Protein: ENSMUSP00000112838
Gene: ENSMUSG00000032511
AA Change: L1666P

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: L1665P

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

SMART Domains

Protein: ENSMUSP00000113272
Gene: ENSMUSG00000032511
AA Change: L1665P

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: 99.5%
20x: 98.2%

Validation Efficiency

98% (58/59)

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: 59 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
6030458C11Rik	T	C	15: 12,812,068	H270R	probably damaging	Het
Abcb1a	T	C	5: 8,701,628	I336T	probably benign	Het
Adam19	T	A	11: 46,112,875	F177I	probably benign	Het
Ankrd53	T	C	6: 83,768,173	V455A	probably damaging	Het
Arrdc1	A	G	2: 24,925,665	S415P	probably benign	Het
Atp10a	T	C	7: 58,797,352	L614P	probably benign	Het
C130060K24Rik	A	T	6: 65,456,336	N380I	probably benign	Het
Catsper1	G	T	19: 5,343,963	V668F	probably damaging	Het
Cluh	T	A	11: 74,661,918	D596E	probably damaging	Het
Cnot10	A	G	9: 114,615,107	S407P	probably benign	Het
Commd6	T	C	14: 101,634,350	T86A	probably damaging	Het
D5Ertd579e	A	T	5: 36,604,657		probably null	Het
Eif3l	A	G	15: 79,085,560	D252G	probably damaging	Het
Epha2	A	T	4: 141,328,468	S962C	probably damaging	Het
Fcho1	C	A	8: 71,714,425		probably null	Het
Fgf23	G	T	6: 127,073,216	G63C	probably damaging	Het
Flnc	A	T	6: 29,445,749	Y834F	probably damaging	Het
Gcn1l1	T	C	5: 115,588,110	L608P	probably damaging	Het
Hdac5	T	A	11: 102,202,276	E545V	probably damaging	Het
Hecw2	A	T	1: 53,937,132	M166K	probably benign	Het
Ikbkb	T	C	8: 22,665,893	D586G	probably damaging	Het
Il1f9	G	C	2: 24,188,621		probably null	Het
Ipo13	A	T	4: 117,904,911	I422N	possibly damaging	Het
Iqgap3	GGAGAG	GGAG	3: 88,112,771		probably null	Het
Kat6a	G	A	8: 22,932,361	A896T	probably benign	Het
Kif28	A	G	1: 179,735,994	I139T	probably damaging	Het
Klhl25	A	G	7: 75,866,342	E332G	probably damaging	Het
Krt8	C	T	15: 101,997,908	A389T	probably benign	Het
Msrb3	T	C	10: 120,784,106	S175G	probably benign	Het
Muc5ac	C	T	7: 141,809,744		probably benign	Het
Myo10	T	C	15: 25,805,659	Y1709H	probably benign	Het
Nckap5	A	G	1: 126,023,194	S1519P	probably benign	Het
Npnt	T	A	3: 132,909,910	D124V	probably damaging	Het
Nr1d1	A	T	11: 98,770,836		probably null	Het
Ogdh	A	G	11: 6,340,477	Y365C	probably benign	Het
Olfr1305	A	T	2: 111,872,961	I298N	possibly damaging	Het
Phf21b	A	T	15: 84,787,446	C416S	probably damaging	Het
Prpsap1	A	G	11: 116,471,438	S373P	probably damaging	Het
Rab28	T	C	5: 41,703,534	T26A	probably damaging	Het
Rbbp8nl	A	G	2: 180,279,226	I455T	probably benign	Het
Rnft2	G	A	5: 118,228,818	A285V	possibly damaging	Het
Rrp36	G	T	17: 46,672,371	Q106K	probably benign	Het
Rsf1	CG	CGACGGCGGAG	7: 97,579,908		probably benign	Het
Runx2	G	A	17: 44,814,192	P80L	probably damaging	Het
Siglecf	A	C	7: 43,355,200	T318P	probably benign	Het
Slc22a1	C	T	17: 12,667,305	W147*	probably null	Het
Smchd1	T	C	17: 71,353,506	I1868V	probably damaging	Het
Snx21	A	G	2: 164,791,902	S203G	probably damaging	Het
Srl	T	C	16: 4,482,831	K792R	probably benign	Het
Srrt	A	G	5: 137,298,673	F100S	probably benign	Het
Stard9	G	T	2: 120,697,436	M1391I	probably benign	Het
Syne2	A	G	12: 76,035,630	E119G	probably damaging	Het
Syt11	G	T	3: 88,762,155	S143R	possibly damaging	Het
Tiparp	T	A	3: 65,531,642	H126Q	probably benign	Het
Tulp2	C	A	7: 45,518,614	T150K	probably benign	Het
Ugt2b37	T	A	5: 87,242,429	Y386F	probably benign	Het
Usp31	C	T	7: 121,649,640	W860*	probably null	Het
Zfp317	A	G	9: 19,643,665	R30G	probably damaging	Het
Zfp709	C	A	8: 71,889,007	N93K	possibly 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
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
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'- GCCACACTGAAGTTCTCCAG -3'
(R):5'- AGTCTTGCTTGTTTCCCACAGG -3'

Sequencing Primer
(F):5'- CACACTGAAGTTCTCCAGGATGATG -3'
(R):5'- AGGCACTGTCCTCTCCGAC -3'

Posted On

2018-10-18