Mutagenetix > Incidental Mutation

Incidental Mutation 'R6133:Scn2a'

487223

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

044280-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R6133 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

65451115-65597791 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

G to A at 65573448 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Valine to Isoleucine at position 1433 (V1433I)

Ref Sequence

ENSEMBL: ENSMUSP00000143882 (fasta)

Gene Model

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

AlphaFold

B1AWN6

Predicted Effect

probably benign
Transcript: ENSMUST00000028377
AA Change: V1433I

PolyPhen 2 Score 0.349 (Sensitivity: 0.90; Specificity: 0.89)

SMART Domains

Protein: ENSMUSP00000028377
Gene: ENSMUSG00000075318
AA Change: V1433I

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 benign
Transcript: ENSMUST00000100067
AA Change: V1433I

PolyPhen 2 Score 0.349 (Sensitivity: 0.90; Specificity: 0.89)

SMART Domains

Protein: ENSMUSP00000097645
Gene: ENSMUSG00000075318
AA Change: V1433I

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 benign
Transcript: ENSMUST00000200829
AA Change: V1433I

PolyPhen 2 Score 0.349 (Sensitivity: 0.90; Specificity: 0.89)

SMART Domains

Protein: ENSMUSP00000143882
Gene: ENSMUSG00000075318
AA Change: V1433I

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

0.0746

Coding Region Coverage

1x: 99.9%
3x: 99.7%
10x: 98.6%
20x: 96.2%

Validation Efficiency

100% (47/47)

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: 45 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Adcy7	A	G	8: 89,052,067 (GRCm39)	T912A	possibly damaging	Het
Akap12	G	T	10: 4,305,178 (GRCm39)	G663C	probably benign	Het
Ankhd1	T	C	18: 36,758,179 (GRCm39)	S958P	possibly damaging	Het
Cmtm2a	T	C	8: 105,019,362 (GRCm39)	I76V	probably benign	Het
Cpxm2	G	A	7: 131,730,182 (GRCm39)	P146S	probably damaging	Het
Cubn	A	G	2: 13,313,429 (GRCm39)	V3047A	probably benign	Het
Dgkd	T	A	1: 87,865,962 (GRCm39)	V198E	possibly damaging	Het
Dnah3	A	T	7: 119,685,469 (GRCm39)	M181K	probably benign	Het
Dnah7a	T	C	1: 53,458,814 (GRCm39)	T3775A	probably benign	Het
Dsg2	A	G	18: 20,723,146 (GRCm39)	I391V	probably benign	Het
Ebi3	T	A	17: 56,261,311 (GRCm39)	V69E	probably benign	Het
Fn1	T	C	1: 71,636,886 (GRCm39)	T1998A	probably damaging	Het
Frmpd1	T	A	4: 45,284,915 (GRCm39)	H1245Q	probably benign	Het
Gm7145	T	A	1: 117,913,618 (GRCm39)	C167S	probably damaging	Het
Hydin	C	T	8: 111,327,908 (GRCm39)	T4805I	probably benign	Het
Itgb4	C	T	11: 115,874,983 (GRCm39)	R447W	probably benign	Het
Kcnma1	C	T	14: 24,053,936 (GRCm39)	M21I	probably damaging	Het
Lrfn5	A	G	12: 61,890,574 (GRCm39)	D621G	probably benign	Het
Lrrc15	C	T	16: 30,093,054 (GRCm39)	G95D	probably benign	Het
Mex3d	A	G	10: 80,222,620 (GRCm39)	L212P	probably damaging	Het
Mmel1	C	T	4: 154,979,475 (GRCm39)	H728Y	probably damaging	Het
Naip1	A	G	13: 100,581,151 (GRCm39)	V32A	probably benign	Het
Nsl1	T	C	1: 190,803,403 (GRCm39)	L158P	probably damaging	Het
Or51q1c	A	T	7: 103,652,532 (GRCm39)	T17S	possibly damaging	Het
Or6c202	G	A	10: 128,996,752 (GRCm39)	L34F	possibly damaging	Het
Or8b36	ATTGCTGTTT	ATTGCTGTTTGCTGTTT	9: 37,937,836 (GRCm39)		probably null	Het
Pakap	C	T	4: 57,855,516 (GRCm39)	Q525*	probably null	Het
Pcdh15	A	T	10: 74,481,805 (GRCm39)		probably null	Het
Pramel15	T	C	4: 144,104,347 (GRCm39)	R53G	possibly damaging	Het
Ptpn1	T	C	2: 167,809,716 (GRCm39)	V108A	possibly damaging	Het
Rad9b	T	C	5: 122,477,831 (GRCm39)	N182D	possibly damaging	Het
Rp1l1	C	T	14: 64,267,545 (GRCm39)	P1044S	probably damaging	Het
Ssrp1	T	G	2: 84,875,683 (GRCm39)		probably benign	Het
Suco	T	A	1: 161,662,752 (GRCm39)	K560*	probably null	Het
Tbx3	T	C	5: 119,819,018 (GRCm39)	V531A	probably benign	Het
Tmem30c	T	C	16: 57,098,100 (GRCm39)	Y107C	probably damaging	Het
Topbp1	T	A	9: 103,188,963 (GRCm39)		probably null	Het
Trpm5	A	T	7: 142,642,688 (GRCm39)	D86E	probably damaging	Het
Urb2	C	T	8: 124,755,300 (GRCm39)	Q336*	probably null	Het
Vmn2r43	A	G	7: 8,247,970 (GRCm39)	F731S	probably damaging	Het
Xkr9	A	G	1: 13,754,359 (GRCm39)	T118A	probably benign	Het
Zcchc2	A	C	1: 105,947,609 (GRCm39)	K117N	probably damaging	Het
Zfp52	T	C	17: 21,780,733 (GRCm39)	Y194H	probably damaging	Het
Zfp763	C	T	17: 33,237,675 (GRCm39)	C490Y	possibly damaging	Het
Zmynd19	G	T	2: 24,848,131 (GRCm39)	R148L	possibly 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
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
R7388:Scn2a	UTSW	2	65,518,998 (GRCm39)	missense	probably damaging	1.00
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'- CACAAACGGACTTGAATGAATCTTG -3'
(R):5'- GAAGGTTCCTATTAGACCTTTTCAC -3'

Sequencing Primer
(F):5'- TGTGCATCTAGAGGAAGCTCATC -3'
(R):5'- TCTTTAACTAAAGAAACGAATCCCC -3'

Posted On

2017-10-10