NM_000335.5(SCN5A):c.3775G>T (p.Ala1259Ser) AND not provided

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 8, 2021
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:: RCV003657658.1

Allele description

NM_000335.5(SCN5A):c.3775G>T (p.Ala1259Ser)

Gene:

SCN5A:sodium voltage-gated channel alpha subunit 5 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p22.2

Genomic location:

Preferred name:

NM_000335.5(SCN5A):c.3775G>T (p.Ala1259Ser)

HGVS:

NC_000003.12:g.38566471C>A
NG_008934.1:g.88202G>T
NM_000335.5:c.3775G>TMANE SELECT
NM_001099404.2:c.3778G>T
NM_001099405.2:c.3778G>T
NM_001160160.2:c.3775G>T
NM_001160161.2:c.3616G>T
NM_001354701.2:c.3775G>T
NM_198056.3:c.3778G>T
NP_000326.2:p.Ala1259Ser
NP_001092874.1:p.Ala1260Ser
NP_001092875.1:p.Ala1260Ser
NP_001153632.1:p.Ala1259Ser
NP_001153633.1:p.Ala1206Ser
NP_001341630.1:p.Ala1259Ser
NP_932173.1:p.Ala1260Ser
LRG_289:g.88202G>T
NC_000003.11:g.38607962C>A

Protein change:

A1206S

Links:

dbSNP: rs2125849662

NCBI 1000 Genomes Browser:

rs2125849662

Molecular consequence:

NM_000335.5:c.3775G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001099404.2:c.3778G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001099405.2:c.3778G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001160160.2:c.3775G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001160161.2:c.3616G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354701.2:c.3775G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_198056.3:c.3778G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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Mus musculus tissue factor pathway inhibitor 2 (Tfpi2), mRNA
Mus musculus tissue factor pathway inhibitor 2 (Tfpi2), mRNA
gi|142382435|ref|NM_009364.3|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002309230	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 8, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002309230

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 8, 2021)

germline

clinical testing

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

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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV002309230.3

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. This variant has not been reported in the literature in individuals affected with SCN5A-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with serine at codon 1260 of the SCN5A protein (p.Ala1260Ser). The alanine residue is highly conserved and there is a moderate physicochemical difference between alanine and serine.

#	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: Sep 16, 2024

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