Mutagenetix > Incidental Mutation

Incidental Mutation 'R3083:Scn1a'

264058

Institutional Source

Beutler Lab

Gene Symbol

Scn1a

Ensembl Gene

ENSMUSG00000064329

Gene Name

sodium channel, voltage-gated, type I, alpha

Synonyms

Nav1.1

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R3083 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

66101125-66271181 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 66129981 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Phenylalanine to Serine at position 1278 (F1278S)

Ref Sequence

ENSEMBL: ENSMUSP00000107990 (fasta)

Gene Model

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

AlphaFold

A2APX8

Predicted Effect

probably damaging
Transcript: ENSMUST00000077489
AA Change: F1278S

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

SMART Domains

Protein: ENSMUSP00000076697
Gene: ENSMUSG00000064329
AA Change: F1278S

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: F1261S

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

SMART Domains

Protein: ENSMUSP00000092558
Gene: ENSMUSG00000064329
AA Change: F1261S

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: F1289S

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

SMART Domains

Protein: ENSMUSP00000107985
Gene: ENSMUSG00000064329
AA Change: F1289S

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

probably damaging
Transcript: ENSMUST00000112371
AA Change: F1278S

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

SMART Domains

Protein: ENSMUSP00000107990
Gene: ENSMUSG00000064329
AA Change: F1278S

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: F258S

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

SMART Domains

Protein: ENSMUSP00000144633
Gene: ENSMUSG00000064329
AA Change: F258S

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

unknown
Transcript: ENSMUST00000200839
AA Change: F193S

Coding Region Coverage

1x: 99.1%
3x: 98.5%
10x: 97.0%
20x: 94.0%

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: 24 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Acss3	A	G	10: 106,859,576 (GRCm39)	V341A	possibly damaging	Het
Armc2	T	C	10: 41,842,726 (GRCm39)	D359G	probably damaging	Het
Cdh6	T	C	15: 13,044,838 (GRCm39)	D428G	probably damaging	Het
Dennd4a	A	G	9: 64,813,363 (GRCm39)	N1441D	probably benign	Het
Fbln1	T	G	15: 85,149,454 (GRCm39)	I617S	probably benign	Het
Gas2l3	CACTCGTCATACT	CACT	10: 89,266,820 (GRCm39)		probably benign	Het
Gm15446	A	G	5: 110,091,158 (GRCm39)	N470S	possibly damaging	Het
Grin3a	G	A	4: 49,665,243 (GRCm39)	R1131W	probably benign	Het
H2bc27	A	G	11: 58,839,802 (GRCm39)	K13E	probably benign	Het
Incenp	T	A	19: 9,861,143 (GRCm39)	M480L	unknown	Het
Lrp1b	A	T	2: 40,490,336 (GRCm39)	M275K	probably damaging	Het
Lrrc14b	C	T	13: 74,511,337 (GRCm39)	D248N	possibly damaging	Het
Nlrp5	T	C	7: 23,129,588 (GRCm39)	F885S	probably benign	Het
Or12d2	T	C	17: 37,625,086 (GRCm39)	N63S	probably damaging	Het
Or4c122	A	C	2: 89,079,345 (GRCm39)	V231G	probably damaging	Het
Or8b52	A	G	9: 38,576,912 (GRCm39)	V76A	probably damaging	Het
Plcl2	T	A	17: 50,994,772 (GRCm39)	N1080K	probably benign	Het
Rab3gap2	T	A	1: 184,936,466 (GRCm39)	S10T	probably benign	Het
Rtca	G	A	3: 116,301,674 (GRCm39)		probably benign	Het
Slitrk3	T	C	3: 72,955,928 (GRCm39)	D948G	probably benign	Het
Smu1	T	C	4: 40,745,567 (GRCm39)	D251G	probably damaging	Het
Ssh3	C	T	19: 4,312,587 (GRCm39)	R586H	probably benign	Het
Tomm40l	A	T	1: 171,048,780 (GRCm39)	L78H	probably damaging	Het
Vmn2r4	A	G	3: 64,296,788 (GRCm39)	S666P	probably damaging	Het

Other mutations in Scn1a

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00513:Scn1a	APN	2	66,165,875 (GRCm39)	critical splice acceptor site	probably null
IGL00650:Scn1a	APN	2	66,111,137 (GRCm39)	missense	probably damaging	1.00
IGL00658:Scn1a	APN	2	66,116,382 (GRCm39)	missense	probably damaging	1.00
IGL00823:Scn1a	APN	2	66,155,279 (GRCm39)	missense	probably benign	0.04
IGL00907:Scn1a	APN	2	66,158,141 (GRCm39)	missense	probably damaging	1.00
IGL01339:Scn1a	APN	2	66,156,304 (GRCm39)	missense	probably benign	0.09
IGL01401:Scn1a	APN	2	66,119,455 (GRCm39)	missense	probably damaging	1.00
IGL01503:Scn1a	APN	2	66,152,687 (GRCm39)	missense	probably damaging	1.00
IGL01575:Scn1a	APN	2	66,103,580 (GRCm39)	missense	probably damaging	1.00
IGL01598:Scn1a	APN	2	66,132,829 (GRCm39)	missense	possibly damaging	0.63
IGL01613:Scn1a	APN	2	66,116,281 (GRCm39)	missense	probably damaging	1.00
IGL01796:Scn1a	APN	2	66,162,645 (GRCm39)	splice site	probably benign
IGL02079:Scn1a	APN	2	66,153,704 (GRCm39)	missense	probably benign	0.14
IGL02171:Scn1a	APN	2	66,103,543 (GRCm39)	missense	probably damaging	1.00
IGL02335:Scn1a	APN	2	66,108,005 (GRCm39)	missense	possibly damaging	0.93
IGL02406:Scn1a	APN	2	66,156,380 (GRCm39)	missense	possibly damaging	0.88
IGL02436:Scn1a	APN	2	66,181,497 (GRCm39)	missense	probably benign	0.01
IGL02507:Scn1a	APN	2	66,108,157 (GRCm39)	missense	probably damaging	1.00
IGL02646:Scn1a	APN	2	66,129,962 (GRCm39)	splice site	probably null
IGL02729:Scn1a	APN	2	66,129,994 (GRCm39)	missense	probably damaging	1.00
IGL02740:Scn1a	APN	2	66,148,421 (GRCm39)	missense	probably benign	0.00
IGL02740:Scn1a	APN	2	66,155,106 (GRCm39)	missense	probably damaging	1.00
IGL02752:Scn1a	APN	2	66,161,756 (GRCm39)	missense	probably damaging	1.00
IGL02815:Scn1a	APN	2	66,155,202 (GRCm39)	missense	probably damaging	1.00
IGL03163:Scn1a	APN	2	66,148,418 (GRCm39)	missense	probably benign	0.00
IGL03229:Scn1a	APN	2	66,130,057 (GRCm39)	missense	probably damaging	1.00
IGL03286:Scn1a	APN	2	66,107,920 (GRCm39)	missense	probably damaging	0.99
IGL03393:Scn1a	APN	2	66,148,362 (GRCm39)	missense	probably benign	0.19
BB008:Scn1a	UTSW	2	66,148,156 (GRCm39)	missense	probably damaging	0.99
BB018:Scn1a	UTSW	2	66,148,156 (GRCm39)	missense	probably damaging	0.99
PIT4791001:Scn1a	UTSW	2	66,103,626 (GRCm39)	missense	probably benign	0.18
R0053:Scn1a	UTSW	2	66,130,119 (GRCm39)	missense	probably benign	0.05
R0053:Scn1a	UTSW	2	66,130,119 (GRCm39)	missense	probably benign	0.05
R0107:Scn1a	UTSW	2	66,154,977 (GRCm39)	missense	probably benign	0.07
R0141:Scn1a	UTSW	2	66,119,406 (GRCm39)	missense	probably damaging	1.00
R0485:Scn1a	UTSW	2	66,104,269 (GRCm39)	missense	probably damaging	0.98
R0517:Scn1a	UTSW	2	66,132,751 (GRCm39)	missense	possibly damaging	0.88
R0532:Scn1a	UTSW	2	66,148,167 (GRCm39)	missense	probably damaging	1.00
R0746:Scn1a	UTSW	2	66,181,470 (GRCm39)	missense	probably benign	0.25
R0755:Scn1a	UTSW	2	66,151,379 (GRCm39)	missense	probably damaging	1.00
R0830:Scn1a	UTSW	2	66,130,128 (GRCm39)	missense	probably damaging	1.00
R0846:Scn1a	UTSW	2	66,155,099 (GRCm39)	missense	probably benign	0.43
R0918:Scn1a	UTSW	2	66,153,651 (GRCm39)	splice site	probably null
R1055:Scn1a	UTSW	2	66,168,340 (GRCm39)	missense	probably benign	0.08
R1432:Scn1a	UTSW	2	66,152,773 (GRCm39)	missense	probably damaging	1.00
R1497:Scn1a	UTSW	2	66,162,631 (GRCm39)	missense	probably damaging	1.00
R1512:Scn1a	UTSW	2	66,161,629 (GRCm39)	missense	possibly damaging	0.82
R1525:Scn1a	UTSW	2	66,149,806 (GRCm39)	nonsense	probably null
R1567:Scn1a	UTSW	2	66,103,675 (GRCm39)	missense	probably damaging	1.00
R1702:Scn1a	UTSW	2	66,148,567 (GRCm39)	missense	probably damaging	1.00
R1744:Scn1a	UTSW	2	66,152,620 (GRCm39)	missense	probably benign	0.06
R1834:Scn1a	UTSW	2	66,154,961 (GRCm39)	missense	probably benign	0.00
R1834:Scn1a	UTSW	2	66,154,960 (GRCm39)	missense	probably benign	0.04
R1860:Scn1a	UTSW	2	66,148,326 (GRCm39)	missense	probably damaging	0.99
R1871:Scn1a	UTSW	2	66,148,369 (GRCm39)	missense	probably damaging	0.98
R1909:Scn1a	UTSW	2	66,161,696 (GRCm39)	missense	possibly damaging	0.58
R1967:Scn1a	UTSW	2	66,158,769 (GRCm39)	missense	probably damaging	1.00
R1976:Scn1a	UTSW	2	66,161,615 (GRCm39)	missense	probably benign	0.02
R2291:Scn1a	UTSW	2	66,119,312 (GRCm39)	missense	probably benign	0.44
R2302:Scn1a	UTSW	2	66,108,089 (GRCm39)	missense	probably damaging	1.00
R2367:Scn1a	UTSW	2	66,158,023 (GRCm39)	missense	probably damaging	1.00
R2418:Scn1a	UTSW	2	66,104,187 (GRCm39)	missense	probably damaging	0.98
R2517:Scn1a	UTSW	2	66,104,176 (GRCm39)	missense	probably damaging	1.00
R2568:Scn1a	UTSW	2	66,103,813 (GRCm39)	missense	probably damaging	1.00
R3903:Scn1a	UTSW	2	66,148,476 (GRCm39)	missense	probably benign	0.08
R3909:Scn1a	UTSW	2	66,104,332 (GRCm39)	missense	probably damaging	1.00
R3916:Scn1a	UTSW	2	66,107,957 (GRCm39)	missense	probably damaging	1.00
R3935:Scn1a	UTSW	2	66,158,120 (GRCm39)	missense	probably damaging	0.99
R3936:Scn1a	UTSW	2	66,158,120 (GRCm39)	missense	probably damaging	0.99
R4043:Scn1a	UTSW	2	66,156,380 (GRCm39)	missense	possibly damaging	0.60
R4429:Scn1a	UTSW	2	66,181,329 (GRCm39)	missense	possibly damaging	0.77
R4495:Scn1a	UTSW	2	66,111,146 (GRCm39)	critical splice acceptor site	probably null
R4662:Scn1a	UTSW	2	66,181,332 (GRCm39)	missense	probably benign	0.23
R4834:Scn1a	UTSW	2	66,158,866 (GRCm39)	nonsense	probably null
R4873:Scn1a	UTSW	2	66,158,820 (GRCm39)	missense	possibly damaging	0.92
R4875:Scn1a	UTSW	2	66,158,820 (GRCm39)	missense	possibly damaging	0.92
R5099:Scn1a	UTSW	2	66,108,145 (GRCm39)	missense	probably damaging	1.00
R5255:Scn1a	UTSW	2	66,108,013 (GRCm39)	missense	probably damaging	0.99
R5435:Scn1a	UTSW	2	66,103,878 (GRCm39)	missense	probably damaging	1.00
R5449:Scn1a	UTSW	2	66,151,346 (GRCm39)	missense	probably damaging	0.96
R5519:Scn1a	UTSW	2	66,162,557 (GRCm39)	missense	probably damaging	1.00
R5541:Scn1a	UTSW	2	66,154,977 (GRCm39)	missense	probably benign	0.07
R5556:Scn1a	UTSW	2	66,155,141 (GRCm39)	missense	probably benign	0.00
R5587:Scn1a	UTSW	2	66,103,425 (GRCm39)	missense	probably benign	0.01
R5972:Scn1a	UTSW	2	66,181,454 (GRCm39)	missense	possibly damaging	0.65
R5992:Scn1a	UTSW	2	66,165,800 (GRCm39)	missense	probably damaging	1.00
R6195:Scn1a	UTSW	2	66,107,962 (GRCm39)	missense	possibly damaging	0.59
R6233:Scn1a	UTSW	2	66,107,962 (GRCm39)	missense	possibly damaging	0.59
R6328:Scn1a	UTSW	2	66,103,660 (GRCm39)	missense	probably damaging	1.00
R6417:Scn1a	UTSW	2	66,103,542 (GRCm39)	missense	probably damaging	1.00
R6420:Scn1a	UTSW	2	66,103,542 (GRCm39)	missense	probably damaging	1.00
R6421:Scn1a	UTSW	2	66,103,271 (GRCm39)	missense	probably damaging	1.00
R6461:Scn1a	UTSW	2	66,156,466 (GRCm39)	missense	probably null	0.01
R6701:Scn1a	UTSW	2	66,168,304 (GRCm39)	missense	probably damaging	0.99
R6717:Scn1a	UTSW	2	66,162,631 (GRCm39)	missense	probably damaging	1.00
R6834:Scn1a	UTSW	2	66,158,086 (GRCm39)	missense	probably damaging	1.00
R6918:Scn1a	UTSW	2	66,162,557 (GRCm39)	missense	probably damaging	1.00
R6953:Scn1a	UTSW	2	66,149,813 (GRCm39)	missense	probably damaging	1.00
R6996:Scn1a	UTSW	2	66,118,075 (GRCm39)	missense	probably damaging	1.00
R7022:Scn1a	UTSW	2	66,148,243 (GRCm39)	missense	probably damaging	1.00
R7109:Scn1a	UTSW	2	66,181,286 (GRCm39)	missense	possibly damaging	0.62
R7115:Scn1a	UTSW	2	66,154,962 (GRCm39)	nonsense	probably null
R7239:Scn1a	UTSW	2	66,108,000 (GRCm39)	splice site	probably null
R7434:Scn1a	UTSW	2	66,103,389 (GRCm39)	missense	probably benign
R7646:Scn1a	UTSW	2	66,118,102 (GRCm39)	missense	possibly damaging	0.93
R7711:Scn1a	UTSW	2	66,134,004 (GRCm39)	missense	probably benign
R7879:Scn1a	UTSW	2	66,116,349 (GRCm39)	nonsense	probably null
R7931:Scn1a	UTSW	2	66,148,156 (GRCm39)	missense	probably damaging	0.99
R7962:Scn1a	UTSW	2	66,158,786 (GRCm39)	missense	probably damaging	1.00
R8025:Scn1a	UTSW	2	66,148,557 (GRCm39)	missense	probably benign	0.02
R8055:Scn1a	UTSW	2	66,149,845 (GRCm39)	missense	probably damaging	1.00
R8095:Scn1a	UTSW	2	66,132,809 (GRCm39)	missense	possibly damaging	0.93
R8167:Scn1a	UTSW	2	66,155,182 (GRCm39)	missense	probably damaging	0.98
R8339:Scn1a	UTSW	2	66,116,373 (GRCm39)	missense	probably damaging	1.00
R8363:Scn1a	UTSW	2	66,152,601 (GRCm39)	missense	probably damaging	1.00
R8516:Scn1a	UTSW	2	66,156,478 (GRCm39)	missense	possibly damaging	0.79
R8559:Scn1a	UTSW	2	66,118,077 (GRCm39)	missense	probably damaging	1.00
R8726:Scn1a	UTSW	2	66,133,983 (GRCm39)	missense	probably benign
R8733:Scn1a	UTSW	2	66,154,944 (GRCm39)	missense	probably benign
R8779:Scn1a	UTSW	2	66,181,257 (GRCm39)	critical splice donor site	probably benign
R8841:Scn1a	UTSW	2	66,156,466 (GRCm39)	missense	probably benign	0.09
R8916:Scn1a	UTSW	2	66,108,127 (GRCm39)	missense	probably damaging	1.00
R8919:Scn1a	UTSW	2	66,168,330 (GRCm39)	missense	probably benign	0.16
R9040:Scn1a	UTSW	2	66,148,245 (GRCm39)	missense	probably damaging	0.99
R9086:Scn1a	UTSW	2	66,181,358 (GRCm39)	missense	probably benign	0.01
R9176:Scn1a	UTSW	2	66,103,689 (GRCm39)	missense	probably damaging	1.00
R9228:Scn1a	UTSW	2	66,130,099 (GRCm39)	missense	probably benign	0.10
R9275:Scn1a	UTSW	2	66,130,026 (GRCm39)	missense	probably damaging	1.00
R9365:Scn1a	UTSW	2	66,148,465 (GRCm39)	missense	probably benign	0.10
R9478:Scn1a	UTSW	2	66,156,493 (GRCm39)	missense	probably benign	0.01
R9560:Scn1a	UTSW	2	66,158,131 (GRCm39)	missense	probably damaging	1.00
R9608:Scn1a	UTSW	2	66,152,687 (GRCm39)	missense	probably benign	0.02
R9624:Scn1a	UTSW	2	66,153,766 (GRCm39)	missense	probably benign
Z1176:Scn1a	UTSW	2	66,156,472 (GRCm39)	missense	possibly damaging	0.92
Z1177:Scn1a	UTSW	2	66,155,296 (GRCm39)	critical splice acceptor site	probably null

Predicted Primers

PCR Primer
(F):5'- AAGACCCAATCTGGAGTCGG -3'
(R):5'- ATCCCAAGGAAATACCATGTGC -3'

Sequencing Primer
(F):5'- ACCCAATCTGGAGTCGGTCAAG -3'
(R):5'- AGCTAGCTGTAAGATTCTAGTAGTG -3'

Posted On

2015-02-05