Mutagenetix > Incidental Mutation

Incidental Mutation 'R7388:Scn2a'

573233

Institutional Source

Beutler Lab

Gene Symbol

Scn2a

Ensembl Gene

ENSMUSG00000075318

Gene Name

sodium channel, voltage-gated, type II, alpha

Synonyms

A230052E19Rik, Nav1.2, Scn2a1

MMRRC Submission

045470-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R7388 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

65451115-65597791 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 65518998 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Valine to Glutamic Acid at position 408 (V408E)

Ref Sequence

ENSEMBL: ENSMUSP00000028377 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000028377] [ENSMUST00000100067] [ENSMUST00000144254] [ENSMUST00000200829]

AlphaFold

B1AWN6

Predicted Effect

probably damaging
Transcript: ENSMUST00000028377
AA Change: V408E

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

SMART Domains

Protein: ENSMUSP00000028377
Gene: ENSMUSG00000075318
AA Change: V408E

Domain	Start	End	E-Value	Type
Pfam:Ion_trans	128	436	2.2e-81	PFAM
low complexity region	450	471	N/A	INTRINSIC
Pfam:Na_trans_cytopl	505	710	9.6e-83	PFAM
Pfam:Ion_trans	759	994	3.6e-57	PFAM
Pfam:Na_trans_assoc	998	1204	1.7e-63	PFAM
Pfam:Ion_trans	1208	1484	3.3e-66	PFAM
Pfam:Ion_trans	1531	1788	2.8e-57	PFAM
Pfam:PKD_channel	1627	1782	8.6e-7	PFAM
IQ	1905	1927	3.59e-3	SMART
low complexity region	1967	1975	N/A	INTRINSIC
low complexity region	1981	2000	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000100067
AA Change: V408E

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

SMART Domains

Protein: ENSMUSP00000097645
Gene: ENSMUSG00000075318
AA Change: V408E

Domain	Start	End	E-Value	Type
Pfam:Ion_trans	157	424	3.3e-75	PFAM
low complexity region	433	448	N/A	INTRINSIC
low complexity region	450	471	N/A	INTRINSIC
Pfam:DUF3451	488	711	2.6e-66	PFAM
Pfam:Ion_trans	794	983	1.1e-47	PFAM
Pfam:Na_trans_assoc	998	1219	3.5e-77	PFAM
Pfam:Ion_trans	1245	1473	4.4e-55	PFAM
PDB:1BYY\|A	1475	1527	3e-31	PDB
Pfam:Ion_trans	1566	1776	2.4e-52	PFAM
Pfam:PKD_channel	1628	1783	3.6e-7	PFAM
IQ	1905	1927	3.59e-3	SMART
low complexity region	1967	1975	N/A	INTRINSIC
low complexity region	1981	2000	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000144254
AA Change: V408E

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

SMART Domains

Protein: ENSMUSP00000117955
Gene: ENSMUSG00000075318
AA Change: V408E

Domain	Start	End	E-Value	Type
Pfam:Ion_trans	128	436	7.2e-81	PFAM
low complexity region	450	471	N/A	INTRINSIC
low complexity region	484	502	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000200829
AA Change: V408E

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

SMART Domains

Protein: ENSMUSP00000143882
Gene: ENSMUSG00000075318
AA Change: V408E

Domain	Start	End	E-Value	Type
Pfam:Ion_trans	128	436	1.2e-79	PFAM
low complexity region	450	471	N/A	INTRINSIC
Pfam:Na_trans_cytopl	505	710	7.1e-80	PFAM
Pfam:Ion_trans	759	994	2.1e-55	PFAM
Pfam:Na_trans_assoc	998	1204	8e-61	PFAM
Pfam:Ion_trans	1208	1484	1.9e-64	PFAM
Pfam:Ion_trans	1531	1788	1.6e-55	PFAM
Pfam:PKD_channel	1627	1782	1.2e-4	PFAM
IQ	1905	1927	1.8e-5	SMART
low complexity region	1967	1975	N/A	INTRINSIC
low complexity region	1981	2000	N/A	INTRINSIC

Meta Mutation Damage Score

0.6467

Coding Region Coverage

1x: 100.0%
3x: 100.0%
10x: 99.8%
20x: 99.3%

Validation Efficiency

100% (63/63)

MGI Phenotype

FUNCTION: Voltage-gated sodium channels are transmembrane glycoprotein complexes composed of a large alpha subunit with four repeat domains, each of which is composed of six membrane-spanning segments, and one or more regulatory beta subunits. Voltage-gated sodium channels are responsible for the generation and propagation of action potentials in neurons and muscle. This gene encodes one member of the sodium channel alpha subunit gene family. In humans, variants of this gene are associated with seizure disorders and autism spectrum disorder. Mice homozygous for a knockout mutation die with severe hypoxia and extensive neuronal cell death, while gain of function mutations result in progressive seizure disorder. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2016]
PHENOTYPE: Homozygotes for a targeted mutation exhibit excess neuronal apoptosis (especially in the brainstem), reduced neuronal sodium channel currents in vitro, and severe hypoxia resulting in neonatal lethality. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 63 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Afg3l2	T	C	18: 67,556,023 (GRCm39)	E436G	probably damaging	Het
Agbl5	T	A	5: 31,060,583 (GRCm39)	L759*	probably null	Het
Ankrd13b	T	C	11: 77,363,583 (GRCm39)	D460G	probably benign	Het
Apol10a	A	G	15: 77,373,225 (GRCm39)	D287G	possibly damaging	Het
Arhgap44	A	T	11: 64,915,094 (GRCm39)	Y391*	probably null	Het
Asz1	G	T	6: 18,074,900 (GRCm39)	S271R	probably benign	Het
AW554918	A	G	18: 25,473,170 (GRCm39)	N325D	probably benign	Het
Brinp2	A	T	1: 158,082,579 (GRCm39)	L247Q	probably damaging	Het
Casz1	A	G	4: 149,036,850 (GRCm39)	D1704G	unknown	Het
Cdk5rap1	G	A	2: 154,202,595 (GRCm39)	R212W	probably damaging	Het
Cdkl2	T	A	5: 92,167,318 (GRCm39)	T444S	probably benign	Het
Cers2	T	G	3: 95,228,656 (GRCm39)	F160V	probably benign	Het
Cfap276	T	C	3: 108,450,815 (GRCm39)	F86L	possibly damaging	Het
Cga	T	A	4: 34,907,076 (GRCm39)	M99K	probably benign	Het
Cspp1	C	T	1: 10,135,572 (GRCm39)	R138*	probably null	Het
Dao	T	G	5: 114,153,273 (GRCm39)	*133E	probably null	Het
Ddx1	A	T	12: 13,275,456 (GRCm39)	C544S	probably null	Het
Dgkq	A	T	5: 108,806,112 (GRCm39)	V98E	probably damaging	Het
Dnah6	T	A	6: 73,169,300 (GRCm39)	T434S	possibly damaging	Het
Dntt	A	G	19: 41,027,418 (GRCm39)	N162D	probably benign	Het
Dpysl5	T	C	5: 30,902,805 (GRCm39)	V79A	probably benign	Het
Efcab3	T	C	11: 104,611,871 (GRCm39)	L571P	probably damaging	Het
Ep300	T	C	15: 81,532,567 (GRCm39)	C1602R	unknown	Het
Flrt3	C	T	2: 140,503,672 (GRCm39)		probably null	Het
Gk2	A	G	5: 97,604,757 (GRCm39)	V27A	probably damaging	Het
Gnpat	T	G	8: 125,614,553 (GRCm39)	M663R	probably benign	Het
Hc	A	T	2: 34,874,859 (GRCm39)		probably null	Het
Il12rb1	A	G	8: 71,263,271 (GRCm39)	Y67C	probably damaging	Het
Ints15	G	A	5: 143,297,600 (GRCm39)	A149V	probably benign	Het
Kmt2b	C	T	7: 30,281,385 (GRCm39)	D1229N	probably damaging	Het
Lamc1	T	C	1: 153,124,822 (GRCm39)	T650A	probably damaging	Het
Lrp1	G	A	10: 127,419,766 (GRCm39)	R948*	probably null	Het
Map3k21	T	C	8: 126,654,336 (GRCm39)	I385T	probably damaging	Het
Mmrn1	T	A	6: 60,953,236 (GRCm39)	S506T	probably benign	Het
Nlrp1a	A	G	11: 71,014,023 (GRCm39)	F409S	probably damaging	Het
Nlrp3	T	A	11: 59,455,892 (GRCm39)	I896N	probably benign	Het
Noxred1	C	A	12: 87,273,799 (GRCm39)	V81L	probably damaging	Het
Nrcam	A	T	12: 44,645,272 (GRCm39)	I1225F	probably damaging	Het
Or2z2	C	T	11: 58,346,481 (GRCm39)	C98Y	probably damaging	Het
Otos	T	A	1: 92,572,241 (GRCm39)		probably null	Het
Pcdh20	A	G	14: 88,706,103 (GRCm39)	I399T	probably benign	Het
Pkhd1	C	T	1: 20,309,528 (GRCm39)	V2807I	not run	Het
Prrx2	A	G	2: 30,770,902 (GRCm39)	E235G	probably damaging	Het
Rab13	T	C	3: 90,128,327 (GRCm39)	I41T	probably damaging	Het
Rai1	A	C	11: 60,080,201 (GRCm39)	T1422P	possibly damaging	Het
Rcn1	C	T	2: 105,222,336 (GRCm39)	V217M	probably damaging	Het
Sec16a	C	T	2: 26,318,376 (GRCm39)	A121T		Het
Slc35d1	A	G	4: 103,046,982 (GRCm39)		probably null	Het
Slc39a6	A	T	18: 24,717,106 (GRCm39)	V642E	probably damaging	Het
Slc6a19	G	A	13: 73,841,203 (GRCm39)	A69V	probably benign	Het
Spink6	A	T	18: 44,215,386 (GRCm39)	T79S	probably damaging	Het
Spire1	T	C	18: 67,652,950 (GRCm39)	D170G	probably damaging	Het
Sugp1	T	C	8: 70,505,269 (GRCm39)	S79P	probably damaging	Het
Syne3	A	G	12: 104,934,167 (GRCm39)	Y201H	probably damaging	Het
Tbc1d10a	T	C	11: 4,155,858 (GRCm39)		probably null	Het
Tmem14a	C	T	1: 21,299,735 (GRCm39)	Q122*	probably null	Het
Tmem161b	C	A	13: 84,370,537 (GRCm39)		probably benign	Het
Trmt61a	A	G	12: 111,645,321 (GRCm39)	I86V	possibly damaging	Het
Tubgcp4	G	A	2: 121,020,447 (GRCm39)		probably null	Het
Vmn1r79	T	A	7: 11,910,668 (GRCm39)	Y183*	probably null	Het
Vmn2r11	A	T	5: 109,202,742 (GRCm39)	W112R	probably benign	Het
Vpreb1a	T	C	16: 16,686,516 (GRCm39)	K125E	probably benign	Het
Wdr6	A	T	9: 108,451,971 (GRCm39)	F637L	probably damaging	Het

Other mutations in Scn2a

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00088:Scn2a	APN	2	65,594,784 (GRCm39)	missense	probably benign
IGL00159:Scn2a	APN	2	65,573,434 (GRCm39)	missense	probably damaging	1.00
IGL00418:Scn2a	APN	2	65,594,866 (GRCm39)	missense	probably benign	0.43
IGL00753:Scn2a	APN	2	65,514,207 (GRCm39)	missense	possibly damaging	0.66
IGL00770:Scn2a	APN	2	65,566,197 (GRCm39)	missense	probably damaging	1.00
IGL00774:Scn2a	APN	2	65,566,197 (GRCm39)	missense	probably damaging	1.00
IGL00847:Scn2a	APN	2	65,501,078 (GRCm39)	missense	probably damaging	1.00
IGL01155:Scn2a	APN	2	65,548,092 (GRCm39)	missense	probably damaging	1.00
IGL01329:Scn2a	APN	2	65,547,852 (GRCm39)	missense	probably benign	0.05
IGL01537:Scn2a	APN	2	65,546,219 (GRCm39)	missense	probably benign	0.00
IGL01672:Scn2a	APN	2	65,582,278 (GRCm39)	missense	probably damaging	1.00
IGL01958:Scn2a	APN	2	65,532,173 (GRCm39)	missense	probably damaging	1.00
IGL02028:Scn2a	APN	2	65,594,002 (GRCm39)	missense	probably damaging	0.96
IGL02142:Scn2a	APN	2	65,546,182 (GRCm39)	missense	probably damaging	1.00
IGL02160:Scn2a	APN	2	65,560,460 (GRCm39)	missense	probably damaging	1.00
IGL02183:Scn2a	APN	2	65,501,947 (GRCm39)	missense	probably benign	0.20
IGL02341:Scn2a	APN	2	65,518,721 (GRCm39)	missense	probably damaging	1.00
IGL02504:Scn2a	APN	2	65,514,228 (GRCm39)	missense	probably benign	0.02
IGL02530:Scn2a	APN	2	65,560,522 (GRCm39)	missense	probably damaging	0.99
IGL02621:Scn2a	APN	2	65,579,223 (GRCm39)	splice site	probably benign
IGL02652:Scn2a	APN	2	65,532,382 (GRCm39)	missense	possibly damaging	0.82
IGL02966:Scn2a	APN	2	65,532,188 (GRCm39)	missense	possibly damaging	0.93
IGL03188:Scn2a	APN	2	65,501,997 (GRCm39)	missense	probably damaging	0.99
IGL03329:Scn2a	APN	2	65,594,973 (GRCm39)	missense	probably benign
IGL03336:Scn2a	APN	2	65,519,088 (GRCm39)	missense	probably damaging	1.00
IGL03391:Scn2a	APN	2	65,594,557 (GRCm39)	missense	probably damaging	1.00
PIT4280001:Scn2a	UTSW	2	65,546,074 (GRCm39)	missense	probably damaging	1.00
PIT4362001:Scn2a	UTSW	2	65,514,182 (GRCm39)	missense	probably benign	0.09
PIT4403001:Scn2a	UTSW	2	65,542,252 (GRCm39)	missense	probably damaging	1.00
PIT4520001:Scn2a	UTSW	2	65,518,763 (GRCm39)	missense	probably damaging	1.00
R0021:Scn2a	UTSW	2	65,500,859 (GRCm39)	missense	possibly damaging	0.51
R0141:Scn2a	UTSW	2	65,542,160 (GRCm39)	missense	probably benign	0.01
R0240:Scn2a	UTSW	2	65,566,118 (GRCm39)	missense	probably benign	0.32
R0240:Scn2a	UTSW	2	65,566,118 (GRCm39)	missense	probably benign	0.32
R0335:Scn2a	UTSW	2	65,512,435 (GRCm39)	missense	probably damaging	1.00
R0508:Scn2a	UTSW	2	65,548,186 (GRCm39)	missense	probably damaging	0.99
R0558:Scn2a	UTSW	2	65,542,269 (GRCm39)	missense	probably benign	0.26
R0600:Scn2a	UTSW	2	65,532,177 (GRCm39)	missense	possibly damaging	0.90
R0667:Scn2a	UTSW	2	65,582,340 (GRCm39)	missense	possibly damaging	0.91
R1178:Scn2a	UTSW	2	65,517,123 (GRCm39)	splice site	probably benign
R1244:Scn2a	UTSW	2	65,593,999 (GRCm39)	missense	probably damaging	0.98
R1386:Scn2a	UTSW	2	65,519,085 (GRCm39)	missense	probably damaging	1.00
R1434:Scn2a	UTSW	2	65,532,335 (GRCm39)	missense	possibly damaging	0.79
R1440:Scn2a	UTSW	2	65,594,938 (GRCm39)	missense	probably benign
R1448:Scn2a	UTSW	2	65,514,189 (GRCm39)	missense	probably benign	0.17
R1460:Scn2a	UTSW	2	65,532,187 (GRCm39)	missense	probably damaging	0.96
R1553:Scn2a	UTSW	2	65,544,180 (GRCm39)	nonsense	probably null
R1642:Scn2a	UTSW	2	65,514,041 (GRCm39)	missense	probably damaging	1.00
R1803:Scn2a	UTSW	2	65,501,111 (GRCm39)	splice site	probably null
R1981:Scn2a	UTSW	2	65,520,514 (GRCm39)	missense	probably damaging	1.00
R2002:Scn2a	UTSW	2	65,512,427 (GRCm39)	missense	probably null	1.00
R2068:Scn2a	UTSW	2	65,582,417 (GRCm39)	missense	probably benign	0.14
R2125:Scn2a	UTSW	2	65,582,423 (GRCm39)	nonsense	probably null
R2126:Scn2a	UTSW	2	65,582,423 (GRCm39)	nonsense	probably null
R2876:Scn2a	UTSW	2	65,546,241 (GRCm39)	missense	possibly damaging	0.64
R2878:Scn2a	UTSW	2	65,518,715 (GRCm39)	missense	probably damaging	1.00
R3113:Scn2a	UTSW	2	65,579,129 (GRCm39)	missense	possibly damaging	0.86
R3749:Scn2a	UTSW	2	65,544,115 (GRCm39)	missense	probably damaging	1.00
R3750:Scn2a	UTSW	2	65,544,115 (GRCm39)	missense	probably damaging	1.00
R3765:Scn2a	UTSW	2	65,513,054 (GRCm39)	missense	possibly damaging	0.51
R3850:Scn2a	UTSW	2	65,512,375 (GRCm39)	missense	probably benign	0.14
R4585:Scn2a	UTSW	2	65,573,395 (GRCm39)	splice site	probably null
R4586:Scn2a	UTSW	2	65,573,395 (GRCm39)	splice site	probably null
R4588:Scn2a	UTSW	2	65,544,111 (GRCm39)	missense	possibly damaging	0.76
R4622:Scn2a	UTSW	2	65,582,371 (GRCm39)	missense	probably benign	0.04
R5108:Scn2a	UTSW	2	65,518,974 (GRCm39)	missense	probably damaging	1.00
R5161:Scn2a	UTSW	2	65,594,935 (GRCm39)	missense	probably benign	0.00
R5235:Scn2a	UTSW	2	65,582,355 (GRCm39)	missense	probably damaging	1.00
R5464:Scn2a	UTSW	2	65,532,100 (GRCm39)	missense	probably damaging	1.00
R5586:Scn2a	UTSW	2	65,537,639 (GRCm39)	nonsense	probably null
R5630:Scn2a	UTSW	2	65,556,709 (GRCm39)	missense	probably damaging	1.00
R5715:Scn2a	UTSW	2	65,547,928 (GRCm39)	missense	probably benign	0.27
R5730:Scn2a	UTSW	2	65,512,882 (GRCm39)	nonsense	probably null
R5734:Scn2a	UTSW	2	65,548,066 (GRCm39)	missense	possibly damaging	0.49
R5779:Scn2a	UTSW	2	65,594,827 (GRCm39)	missense	probably benign	0.00
R6133:Scn2a	UTSW	2	65,573,448 (GRCm39)	missense	probably benign	0.35
R6547:Scn2a	UTSW	2	65,546,241 (GRCm39)	missense	probably benign	0.29
R6549:Scn2a	UTSW	2	65,595,018 (GRCm39)	missense	probably benign	0.05
R6818:Scn2a	UTSW	2	65,519,013 (GRCm39)	nonsense	probably null
R6999:Scn2a	UTSW	2	65,512,453 (GRCm39)	missense	probably benign
R7069:Scn2a	UTSW	2	65,594,950 (GRCm39)	missense	probably benign	0.00
R7073:Scn2a	UTSW	2	65,558,787 (GRCm39)	missense	probably benign	0.00
R7125:Scn2a	UTSW	2	65,594,277 (GRCm39)	missense	probably damaging	1.00
R7178:Scn2a	UTSW	2	65,579,197 (GRCm39)	nonsense	probably null
R7179:Scn2a	UTSW	2	65,532,323 (GRCm39)	missense	probably damaging	1.00
R7203:Scn2a	UTSW	2	65,578,663 (GRCm39)	missense	probably benign	0.01
R7227:Scn2a	UTSW	2	65,582,367 (GRCm39)	missense	probably damaging	0.98
R7269:Scn2a	UTSW	2	65,594,113 (GRCm39)	missense	probably damaging	1.00
R7358:Scn2a	UTSW	2	65,512,850 (GRCm39)	nonsense	probably null
R7491:Scn2a	UTSW	2	65,532,352 (GRCm39)	missense	probably damaging	0.99
R7619:Scn2a	UTSW	2	65,546,247 (GRCm39)	missense	probably damaging	1.00
R7695:Scn2a	UTSW	2	65,542,251 (GRCm39)	missense	probably damaging	0.99
R7735:Scn2a	UTSW	2	65,594,013 (GRCm39)	missense	probably benign	0.40
R7911:Scn2a	UTSW	2	65,512,427 (GRCm39)	missense	probably null	1.00
R8096:Scn2a	UTSW	2	65,594,366 (GRCm39)	missense	probably damaging	0.98
R8172:Scn2a	UTSW	2	65,520,672 (GRCm39)	missense	probably benign	0.01
R8220:Scn2a	UTSW	2	65,520,620 (GRCm39)	missense	probably benign	0.01
R8333:Scn2a	UTSW	2	65,514,191 (GRCm39)	missense	probably benign	0.01
R8416:Scn2a	UTSW	2	65,511,345 (GRCm39)	missense	probably benign	0.00
R8850:Scn2a	UTSW	2	65,518,730 (GRCm39)	missense	probably damaging	1.00
R8897:Scn2a	UTSW	2	65,546,002 (GRCm39)	critical splice acceptor site	probably null
R8977:Scn2a	UTSW	2	65,594,014 (GRCm39)	missense	probably damaging	0.99
R8992:Scn2a	UTSW	2	65,594,242 (GRCm39)	missense	probably damaging	1.00
R9190:Scn2a	UTSW	2	65,511,346 (GRCm39)	missense	probably benign	0.00
R9206:Scn2a	UTSW	2	65,548,131 (GRCm39)	missense	probably damaging	1.00
R9355:Scn2a	UTSW	2	65,594,433 (GRCm39)	missense	probably damaging	1.00
R9452:Scn2a	UTSW	2	65,595,163 (GRCm39)	missense	probably benign
R9529:Scn2a	UTSW	2	65,594,932 (GRCm39)	missense	probably damaging	0.99
R9567:Scn2a	UTSW	2	65,518,974 (GRCm39)	missense	probably damaging	1.00
R9569:Scn2a	UTSW	2	65,560,622 (GRCm39)	missense	probably damaging	1.00
R9657:Scn2a	UTSW	2	65,566,032 (GRCm39)	missense	probably damaging	1.00
R9715:Scn2a	UTSW	2	65,579,149 (GRCm39)	missense	possibly damaging	0.93
R9761:Scn2a	UTSW	2	65,566,030 (GRCm39)	missense	probably damaging	1.00
Z1176:Scn2a	UTSW	2	65,582,212 (GRCm39)	missense	possibly damaging	0.84
Z1177:Scn2a	UTSW	2	65,548,079 (GRCm39)	missense	probably benign	0.07

Predicted Primers

PCR Primer
(F):5'- AGGAAGCATGAGACTCTTGACC -3'
(R):5'- CAATGTCAACAGCAGCCTTC -3'

Sequencing Primer
(F):5'- TCTTGACCAAGGGAACTGCTG -3'
(R):5'- GTCAACAGCAGCCTTCAGGTC -3'

Posted On

2019-09-13