NM_001165963.4(SCN1A):c.3776T>C (p.Phe1259Ser) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 15, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV003155068.8

Allele description [Variation Report for NM_001165963.4(SCN1A):c.3776T>C (p.Phe1259Ser)]

NM_001165963.4(SCN1A):c.3776T>C (p.Phe1259Ser)

Genes:

SCN1A:sodium voltage-gated channel alpha subunit 1 [Gene - OMIM - HGNC]
LOC102724058:uncharacterized LOC102724058 [Gene]

Variant type:

single nucleotide variant

Cytogenetic location:

2q24.3

Genomic location:

Preferred name:

NM_001165963.4(SCN1A):c.3776T>C (p.Phe1259Ser)

Other names:

p.F1259S:TTC>TCC

HGVS:

NC_000002.12:g.166012212A>G
NG_011906.1:g.66428T>C
NM_001165963.4:c.3776T>CMANE SELECT
NM_001165963.4:c.3776T>C
NM_001165964.3:c.3692T>C
NM_001202435.3:c.3776T>C
NM_001353948.2:c.3776T>C
NM_001353949.2:c.3743T>C
NM_001353950.2:c.3743T>C
NM_001353951.2:c.3743T>C
NM_001353952.2:c.3743T>C
NM_001353954.2:c.3740T>C
NM_001353955.2:c.3740T>C
NM_001353957.2:c.3692T>C
NM_001353958.2:c.3692T>C
NM_001353960.2:c.3689T>C
NM_001353961.2:c.1334T>C
NM_006920.6:c.3743T>C
NP_001159435.1:p.Phe1259Ser
NP_001159436.1:p.Phe1231Ser
NP_001189364.1:p.Phe1259Ser
NP_001340877.1:p.Phe1259Ser
NP_001340878.1:p.Phe1248Ser
NP_001340879.1:p.Phe1248Ser
NP_001340880.1:p.Phe1248Ser
NP_001340881.1:p.Phe1248Ser
NP_001340883.1:p.Phe1247Ser
NP_001340884.1:p.Phe1247Ser
NP_001340886.1:p.Phe1231Ser
NP_001340887.1:p.Phe1231Ser
NP_001340889.1:p.Phe1230Ser
NP_001340890.1:p.Phe445Ser
NP_008851.3:p.Phe1248Ser
LRG_8:g.66428T>C
NC_000002.11:g.166868722A>G
NC_000002.11:g.166868722A>G
NM_001165963.1:c.3776T>C
NR_148667.2:n.4129T>C

Protein change:

F1230S

Links:

dbSNP: rs398123591

NCBI 1000 Genomes Browser:

rs398123591

Molecular consequence:

NM_001165963.4:c.3776T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001165964.3:c.3692T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001202435.3:c.3776T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353948.2:c.3776T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353949.2:c.3743T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353950.2:c.3743T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353951.2:c.3743T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353952.2:c.3743T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353954.2:c.3740T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353955.2:c.3740T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353957.2:c.3692T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353958.2:c.3692T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353960.2:c.3689T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353961.2:c.1334T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_006920.6:c.3743T>C - missense variant - [Sequence Ontology: SO:0001583]
NR_148667.2:n.4129T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003844783	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Feb 15, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003844783

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Feb 15, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Diagnostic outcomes for genetic testing of 70 genes in 8565 patients with epilepsy and neurodevelopmental disorders.

Lindy AS, Stosser MB, Butler E, Downtain-Pickersgill C, Shanmugham A, Retterer K, Brandt T, Richard G, McKnight DA.

Epilepsia. 2018 May;59(5):1062-1071. doi: 10.1111/epi.14074. Epub 2018 Apr 14.

PubMed [citation]

PMID:: 29655203

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV003844783.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

Variant summary: SCN1A c.3776T>C (p.Phe1259Ser) results in a non-conservative amino acid change located in the ion transport domain (IPR005821) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 249954 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.3776T>C has been reported in the literature in at least one individual affected with epilepsy (Lindy_2018). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as pathogenic (n=1)/likely pathogenic (n=2), or VUS (n=1). Based on the evidence outlined above, the variant was classified as uncertain significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jun 9, 2024

ClinVar

Relating variation to medicine