Mutagenetix > Incidental Mutation

Incidental Mutation 'R9275:Scn1a'

703205

Institutional Source

Beutler Lab

Gene Symbol

Scn1a

Ensembl Gene

ENSMUSG00000064329

Gene Name

sodium channel, voltage-gated, type I, alpha

Synonyms

Nav1.1

Accession Numbers

Is this an essential gene?

Essential (E-score: 1.000) question?

Stock #

R9275 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

66270778-66440840 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 66299682 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Tyrosine to Phenylalanine at position 243 (Y243F)

Ref Sequence

ENSEMBL: ENSMUSP00000144633 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000077489] [ENSMUST00000094951] [ENSMUST00000112366] [ENSMUST00000112371] [ENSMUST00000156865]

AlphaFold

A2APX8

Predicted Effect

possibly damaging
Transcript: ENSMUST00000077489
AA Change: Y1263F

PolyPhen 2 Score 0.891 (Sensitivity: 0.82; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000076697
Gene: ENSMUSG00000064329
AA Change: Y1263F

Domain	Start	End	E-Value	Type
low complexity region	23	52	N/A	INTRINSIC
Pfam:Ion_trans	156	422	5.4e-77	PFAM
low complexity region	431	466	N/A	INTRINSIC
Pfam:DUF3451	484	708	5.5e-73	PFAM
Pfam:Ion_trans	791	980	6.8e-47	PFAM
Pfam:Na_trans_assoc	995	1217	1.2e-74	PFAM
Pfam:Ion_trans	1243	1471	1.1e-56	PFAM
PDB:1BYY\|A	1473	1525	4e-31	PDB
Pfam:Ion_trans	1564	1774	1.1e-51	PFAM
Pfam:PKD_channel	1623	1781	3.9e-7	PFAM
low complexity region	1826	1838	N/A	INTRINSIC
IQ	1903	1925	1.65e-2	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000094951
AA Change: Y1246F

PolyPhen 2 Score 0.989 (Sensitivity: 0.72; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000092558
Gene: ENSMUSG00000064329
AA Change: Y1246F

Domain	Start	End	E-Value	Type
low complexity region	23	52	N/A	INTRINSIC
Pfam:Ion_trans	156	422	5.3e-77	PFAM
low complexity region	431	466	N/A	INTRINSIC
Pfam:DUF3451	484	691	2e-62	PFAM
Pfam:Ion_trans	774	963	6.7e-47	PFAM
Pfam:Na_trans_assoc	978	1200	1.2e-74	PFAM
Pfam:Ion_trans	1226	1454	1e-56	PFAM
PDB:1BYY\|A	1456	1508	4e-31	PDB
Pfam:Ion_trans	1547	1757	1.1e-51	PFAM
Pfam:PKD_channel	1606	1764	3.8e-7	PFAM
low complexity region	1809	1821	N/A	INTRINSIC
IQ	1886	1908	1.65e-2	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000112366
AA Change: Y1274F

PolyPhen 2 Score 0.990 (Sensitivity: 0.72; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000107985
Gene: ENSMUSG00000064329
AA Change: Y1274F

Domain	Start	End	E-Value	Type
low complexity region	23	52	N/A	INTRINSIC
Pfam:Ion_trans	127	434	2.8e-82	PFAM
Pfam:Na_trans_cytopl	502	718	2e-91	PFAM
Pfam:Ion_trans	767	1002	6.5e-57	PFAM
Pfam:Na_trans_assoc	1006	1213	1.2e-60	PFAM
Pfam:Ion_trans	1217	1493	3.3e-67	PFAM
Pfam:Ion_trans	1540	1797	6.3e-56	PFAM
Pfam:PKD_channel	1637	1791	1.1e-6	PFAM
low complexity region	1837	1849	N/A	INTRINSIC
IQ	1914	1936	1.65e-2	SMART

Predicted Effect

possibly damaging
Transcript: ENSMUST00000112371
AA Change: Y1263F

PolyPhen 2 Score 0.891 (Sensitivity: 0.82; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000107990
Gene: ENSMUSG00000064329
AA Change: Y1263F

Domain	Start	End	E-Value	Type
low complexity region	23	52	N/A	INTRINSIC
Pfam:Ion_trans	156	422	5.4e-77	PFAM
low complexity region	431	466	N/A	INTRINSIC
Pfam:DUF3451	484	708	5.5e-73	PFAM
Pfam:Ion_trans	791	980	6.8e-47	PFAM
Pfam:Na_trans_assoc	995	1217	1.2e-74	PFAM
Pfam:Ion_trans	1243	1471	1.1e-56	PFAM
PDB:1BYY\|A	1473	1525	4e-31	PDB
Pfam:Ion_trans	1564	1774	1.1e-51	PFAM
Pfam:PKD_channel	1623	1781	3.9e-7	PFAM
low complexity region	1826	1838	N/A	INTRINSIC
IQ	1903	1925	1.65e-2	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000156865
AA Change: Y243F

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

SMART Domains

Protein: ENSMUSP00000144633
Gene: ENSMUSG00000064329
AA Change: Y243F

Domain	Start	End	E-Value	Type
Pfam:Na_trans_assoc	1	182	2.2e-44	PFAM
Pfam:Ion_trans	186	462	1.3e-66	PFAM

Predicted Effect

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.6%
20x: 98.6%

Validation Efficiency

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] Voltage-dependent sodium channels are heteromeric complexes that regulate sodium exchange between intracellular and extracellular spaces and are essential for the generation and propagation of action potentials in muscle cells and neurons. Each sodium channel is composed of a large pore-forming, glycosylated alpha subunit and two smaller beta subunits. This gene encodes a sodium channel alpha subunit, which has four homologous domains, each of which contains six transmembrane regions. Allelic variants of this gene are associated with generalized epilepsy with febrile seizures and epileptic encephalopathy. Alternative splicing results in multiple transcript variants. The RefSeq Project has decided to create four representative RefSeq records. Three of the transcript variants are supported by experimental evidence and the fourth contains alternate 5' untranslated exons, the exact combination of which have not been experimentally confirmed for the full-length transcript. [provided by RefSeq, Oct 2015]
PHENOTYPE: Homozygous null mice show postnatal lethality, seizures and behavioral deficits whereas heterozygotes die prematurely with seizures and abnormal electrophysiology. In addition, knock-in mice exhibit increased susceptibility to febrile and flurothyl-induced seizures, and reduced inhibitory signaling. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 66 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abr	A	G	11: 76,464,282	Y249H	probably damaging	Het
AF067063	T	C	13: 119,828,457	S68G	possibly damaging	Het
Afdn	T	A	17: 13,804,008	C59S	probably damaging	Het
Akap11	C	A	14: 78,513,709	V413F		Het
Ank3	T	C	10: 69,986,832	S444P	probably damaging	Het
Ankrd12	C	T	17: 66,037,604	E91K	possibly damaging	Het
Arhgap10	A	G	8: 77,411,036	S309P	probably damaging	Het
Arpc2	C	A	1: 74,236,882	F19L	probably benign	Het
Atp5a1	C	T	18: 77,781,297	T457I	probably damaging	Het
Bsn	C	T	9: 108,111,620	R2311H	probably damaging	Het
C1ra	A	G	6: 124,517,424	T277A	probably benign	Het
Celsr3	C	G	9: 108,838,490	L2124V	probably benign	Het
Cenpv	T	C	11: 62,525,163	*253W	probably null	Het
Cfap54	A	T	10: 93,039,186	V479E	possibly damaging	Het
Cmpk2	A	T	12: 26,469,569	Y73F	probably benign	Het
Cpne2	T	C	8: 94,555,015	I226T	possibly damaging	Het
Cyp2c67	C	T	19: 39,609,255	R433Q	probably damaging	Het
Dagla	A	G	19: 10,254,856	Y489H	probably damaging	Het
Dennd4a	C	A	9: 64,842,624	P166T	probably damaging	Het
Dnm2	C	T	9: 21,505,681	R837W	possibly damaging	Het
Enpp2	C	T	15: 54,850,088	R658Q	probably benign	Het
Gm10521	G	A	1: 171,896,463	V114I	unknown	Het
Gm7534	A	G	4: 134,195,459	L521P	probably damaging	Het
H2-T24	T	A	17: 36,017,384	E69V	probably damaging	Het
H6pd	T	A	4: 149,995,850	K179N	probably damaging	Het
Hsf2bp	C	T	17: 31,987,362	W265*	probably null	Het
Igfn1	C	A	1: 135,973,447	R431L	probably damaging	Het
Kcng2	T	C	18: 80,295,859	S405G	possibly damaging	Het
Leng9	T	C	7: 4,148,448	T410A	probably benign	Het
Lrp1b	T	C	2: 40,597,064	Y4557C		Het
Ltbp2	G	A	12: 84,791,090	P1192L	probably benign	Het
Mlkl	A	G	8: 111,316,423	V364A	probably benign	Het
Mns1	T	A	9: 72,449,225	F254Y	probably benign	Het
Naip1	T	A	13: 100,426,176	N827I	probably damaging	Het
Neb	C	T	2: 52,256,178	R2929H	probably damaging	Het
Olfr1025-ps1	A	G	2: 85,918,702	Y259C	probably benign	Het
Olfr111	T	A	17: 37,530,928	M317K	probably benign	Het
Pde10a	A	G	17: 8,981,656	*797W	probably null	Het
Pirb	T	G	7: 3,716,860	H429P	probably benign	Het
Plbd1	A	G	6: 136,617,288	L321P	probably damaging	Het
Pmfbp1	A	G	8: 109,535,839	I722V	probably benign	Het
Polr2b	A	G	5: 77,323,638	R274G	probably damaging	Het
Prune2	C	T	19: 17,123,780	T2216I	probably benign	Het
Psma3	A	T	12: 70,994,382	D252V	probably benign	Het
Ptpn1	C	T	2: 167,974,256	T230I	probably damaging	Het
Rhpn1	T	C	15: 75,713,271	V519A	possibly damaging	Het
Rnf213	T	C	11: 119,435,942	V1586A		Het
Rrp36	T	A	17: 46,672,380	K103*	probably null	Het
Rsf1	CGGCGGCGG	CGGCGGCGGGGGCGGCGG	7: 97,579,923		probably benign	Het
Ryr2	T	C	13: 11,883,090	T140A	probably benign	Het
Sdk1	A	G	5: 141,956,198	T534A	possibly damaging	Het
Slc27a5	T	C	7: 12,997,713	D117G	probably damaging	Het
Slc2a1	A	T	4: 119,133,410	E246D	probably benign	Het
Smpd2	T	C	10: 41,487,689	D289G	probably benign	Het
Spag6	A	C	2: 18,699,174	E11A	probably benign	Het
Stard3	G	A	11: 98,372,105		probably benign	Het
Tcf19	A	G	17: 35,515,002	V86A	probably damaging	Het
Tigit	A	T	16: 43,659,470	M154K	probably benign	Het
Trim34a	T	A	7: 104,260,994	N334K	probably damaging	Het
Tsen15	T	C	1: 152,383,347	I87V	probably damaging	Het
Ttn	A	T	2: 76,907,874	M4153K	unknown	Het
Uchl3	A	T	14: 101,668,527		probably null	Het
Usp1	A	G	4: 98,931,341	K347E	probably damaging	Het
Vmn1r73	T	C	7: 11,756,552	M99T	probably benign	Het
Vmn2r20	A	G	6: 123,385,435	W797R	probably damaging	Het
Vwa7	A	G	17: 35,019,736	T267A	probably damaging	Het

Other mutations in Scn1a

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00513:Scn1a	APN	2	66335531	critical splice acceptor site	probably null
IGL00650:Scn1a	APN	2	66280793	missense	probably damaging	1.00
IGL00658:Scn1a	APN	2	66286038	missense	probably damaging	1.00
IGL00823:Scn1a	APN	2	66324935	missense	probably benign	0.04
IGL00907:Scn1a	APN	2	66327797	missense	probably damaging	1.00
IGL01339:Scn1a	APN	2	66325960	missense	probably benign	0.09
IGL01401:Scn1a	APN	2	66289111	missense	probably damaging	1.00
IGL01503:Scn1a	APN	2	66322343	missense	probably damaging	1.00
IGL01575:Scn1a	APN	2	66273236	missense	probably damaging	1.00
IGL01598:Scn1a	APN	2	66302485	missense	possibly damaging	0.63
IGL01613:Scn1a	APN	2	66285937	missense	probably damaging	1.00
IGL01796:Scn1a	APN	2	66332301	splice site	probably benign
IGL02079:Scn1a	APN	2	66323360	missense	probably benign	0.14
IGL02171:Scn1a	APN	2	66273199	missense	probably damaging	1.00
IGL02335:Scn1a	APN	2	66277661	missense	possibly damaging	0.93
IGL02406:Scn1a	APN	2	66326036	missense	possibly damaging	0.88
IGL02436:Scn1a	APN	2	66351153	missense	probably benign	0.01
IGL02507:Scn1a	APN	2	66277813	missense	probably damaging	1.00
IGL02646:Scn1a	APN	2	66299618	splice site	probably null
IGL02729:Scn1a	APN	2	66299650	missense	probably damaging	1.00
IGL02740:Scn1a	APN	2	66324762	missense	probably damaging	1.00
IGL02740:Scn1a	APN	2	66318077	missense	probably benign	0.00
IGL02752:Scn1a	APN	2	66331412	missense	probably damaging	1.00
IGL02815:Scn1a	APN	2	66324858	missense	probably damaging	1.00
IGL03163:Scn1a	APN	2	66318074	missense	probably benign	0.00
IGL03229:Scn1a	APN	2	66299713	missense	probably damaging	1.00
IGL03286:Scn1a	APN	2	66277576	missense	probably damaging	0.99
IGL03393:Scn1a	APN	2	66318018	missense	probably benign	0.19
BB008:Scn1a	UTSW	2	66317812	missense	probably damaging	0.99
BB018:Scn1a	UTSW	2	66317812	missense	probably damaging	0.99
PIT4791001:Scn1a	UTSW	2	66273282	missense	probably benign	0.18
R0053:Scn1a	UTSW	2	66299775	missense	probably benign	0.05
R0053:Scn1a	UTSW	2	66299775	missense	probably benign	0.05
R0107:Scn1a	UTSW	2	66324633	missense	probably benign	0.07
R0141:Scn1a	UTSW	2	66289062	missense	probably damaging	1.00
R0485:Scn1a	UTSW	2	66273925	missense	probably damaging	0.98
R0517:Scn1a	UTSW	2	66302407	missense	possibly damaging	0.88
R0532:Scn1a	UTSW	2	66317823	missense	probably damaging	1.00
R0746:Scn1a	UTSW	2	66351126	missense	probably benign	0.25
R0755:Scn1a	UTSW	2	66321035	missense	probably damaging	1.00
R0830:Scn1a	UTSW	2	66299784	missense	probably damaging	1.00
R0846:Scn1a	UTSW	2	66324755	missense	probably benign	0.43
R0918:Scn1a	UTSW	2	66323307	splice site	probably null
R1055:Scn1a	UTSW	2	66337996	missense	probably benign	0.08
R1432:Scn1a	UTSW	2	66322429	missense	probably damaging	1.00
R1497:Scn1a	UTSW	2	66332287	missense	probably damaging	1.00
R1512:Scn1a	UTSW	2	66331285	missense	possibly damaging	0.82
R1525:Scn1a	UTSW	2	66319462	nonsense	probably null
R1567:Scn1a	UTSW	2	66273331	missense	probably damaging	1.00
R1702:Scn1a	UTSW	2	66318223	missense	probably damaging	1.00
R1744:Scn1a	UTSW	2	66322276	missense	probably benign	0.06
R1834:Scn1a	UTSW	2	66324616	missense	probably benign	0.04
R1834:Scn1a	UTSW	2	66324617	missense	probably benign	0.00
R1860:Scn1a	UTSW	2	66317982	missense	probably damaging	0.99
R1871:Scn1a	UTSW	2	66318025	missense	probably damaging	0.98
R1909:Scn1a	UTSW	2	66331352	missense	possibly damaging	0.58
R1967:Scn1a	UTSW	2	66328425	missense	probably damaging	1.00
R1976:Scn1a	UTSW	2	66331271	missense	probably benign	0.02
R2291:Scn1a	UTSW	2	66288968	missense	probably benign	0.44
R2302:Scn1a	UTSW	2	66277745	missense	probably damaging	1.00
R2367:Scn1a	UTSW	2	66327679	missense	probably damaging	1.00
R2418:Scn1a	UTSW	2	66273843	missense	probably damaging	0.98
R2517:Scn1a	UTSW	2	66273832	missense	probably damaging	1.00
R2568:Scn1a	UTSW	2	66273469	missense	probably damaging	1.00
R3083:Scn1a	UTSW	2	66299637	missense	probably damaging	1.00
R3903:Scn1a	UTSW	2	66318132	missense	probably benign	0.08
R3909:Scn1a	UTSW	2	66273988	missense	probably damaging	1.00
R3916:Scn1a	UTSW	2	66277613	missense	probably damaging	1.00
R3935:Scn1a	UTSW	2	66327776	missense	probably damaging	0.99
R3936:Scn1a	UTSW	2	66327776	missense	probably damaging	0.99
R4043:Scn1a	UTSW	2	66326036	missense	possibly damaging	0.60
R4429:Scn1a	UTSW	2	66350985	missense	possibly damaging	0.77
R4495:Scn1a	UTSW	2	66280802	critical splice acceptor site	probably null
R4662:Scn1a	UTSW	2	66350988	missense	probably benign	0.23
R4834:Scn1a	UTSW	2	66328522	nonsense	probably null
R4873:Scn1a	UTSW	2	66328476	missense	possibly damaging	0.92
R4875:Scn1a	UTSW	2	66328476	missense	possibly damaging	0.92
R5099:Scn1a	UTSW	2	66277801	missense	probably damaging	1.00
R5255:Scn1a	UTSW	2	66277669	missense	probably damaging	0.99
R5435:Scn1a	UTSW	2	66273534	missense	probably damaging	1.00
R5449:Scn1a	UTSW	2	66321002	missense	probably damaging	0.96
R5519:Scn1a	UTSW	2	66332213	missense	probably damaging	1.00
R5541:Scn1a	UTSW	2	66324633	missense	probably benign	0.07
R5556:Scn1a	UTSW	2	66324797	missense	probably benign	0.00
R5587:Scn1a	UTSW	2	66273081	missense	probably benign	0.01
R5972:Scn1a	UTSW	2	66351110	missense	possibly damaging	0.65
R5992:Scn1a	UTSW	2	66335456	missense	probably damaging	1.00
R6195:Scn1a	UTSW	2	66277618	missense	possibly damaging	0.59
R6233:Scn1a	UTSW	2	66277618	missense	possibly damaging	0.59
R6328:Scn1a	UTSW	2	66273316	missense	probably damaging	1.00
R6417:Scn1a	UTSW	2	66273198	missense	probably damaging	1.00
R6420:Scn1a	UTSW	2	66273198	missense	probably damaging	1.00
R6421:Scn1a	UTSW	2	66272927	missense	probably damaging	1.00
R6461:Scn1a	UTSW	2	66326122	missense	probably null	0.01
R6701:Scn1a	UTSW	2	66337960	missense	probably damaging	0.99
R6717:Scn1a	UTSW	2	66332287	missense	probably damaging	1.00
R6834:Scn1a	UTSW	2	66327742	missense	probably damaging	1.00
R6918:Scn1a	UTSW	2	66332213	missense	probably damaging	1.00
R6953:Scn1a	UTSW	2	66319469	missense	probably damaging	1.00
R6996:Scn1a	UTSW	2	66287731	missense	probably damaging	1.00
R7022:Scn1a	UTSW	2	66317899	missense	probably damaging	1.00
R7109:Scn1a	UTSW	2	66350942	missense	possibly damaging	0.62
R7115:Scn1a	UTSW	2	66324618	nonsense	probably null
R7239:Scn1a	UTSW	2	66277656	splice site	probably null
R7434:Scn1a	UTSW	2	66273045	missense	probably benign
R7646:Scn1a	UTSW	2	66287758	missense	possibly damaging	0.93
R7711:Scn1a	UTSW	2	66303660	missense	probably benign
R7879:Scn1a	UTSW	2	66286005	nonsense	probably null
R7931:Scn1a	UTSW	2	66317812	missense	probably damaging	0.99
R7962:Scn1a	UTSW	2	66328442	missense	probably damaging	1.00
R8025:Scn1a	UTSW	2	66318213	missense	probably benign	0.02
R8055:Scn1a	UTSW	2	66319501	missense	probably damaging	1.00
R8095:Scn1a	UTSW	2	66302465	missense	possibly damaging	0.93
R8167:Scn1a	UTSW	2	66324838	missense	probably damaging	0.98
R8339:Scn1a	UTSW	2	66286029	missense	probably damaging	1.00
R8363:Scn1a	UTSW	2	66322257	missense	probably damaging	1.00
R8516:Scn1a	UTSW	2	66326134	missense	possibly damaging	0.79
R8559:Scn1a	UTSW	2	66287733	missense	probably damaging	1.00
R8726:Scn1a	UTSW	2	66303639	missense	probably benign
R8733:Scn1a	UTSW	2	66324600	missense	probably benign
R8779:Scn1a	UTSW	2	66350913	critical splice donor site	probably benign
R8841:Scn1a	UTSW	2	66326122	missense	probably benign	0.09
R8916:Scn1a	UTSW	2	66277783	missense	probably damaging	1.00
R8919:Scn1a	UTSW	2	66337986	missense	probably benign	0.16
R9040:Scn1a	UTSW	2	66317901	missense	probably damaging	0.99
R9086:Scn1a	UTSW	2	66351014	missense	probably benign	0.01
R9176:Scn1a	UTSW	2	66273345	missense	probably damaging	1.00
R9228:Scn1a	UTSW	2	66299755	missense	probably benign	0.10
R9365:Scn1a	UTSW	2	66318121	missense	probably benign	0.10
R9478:Scn1a	UTSW	2	66326149	missense	probably benign	0.01
R9560:Scn1a	UTSW	2	66327787	missense	not run
Z1176:Scn1a	UTSW	2	66326128	missense	possibly damaging	0.92
Z1177:Scn1a	UTSW	2	66324952	critical splice acceptor site	probably null

Predicted Primers

PCR Primer
(F):5'- CTGGGGAGCCTATCTTGTCATC -3'
(R):5'- CGTTCTTCCATCCCAAGGAAATACC -3'

Sequencing Primer
(F):5'- GGGAGCCTATCTTGTCATCACAAC -3'
(R):5'- TTCCATCCCAAGGAAATACCATGTG -3'

Posted On

2022-03-25