U.S. flag

An official website of the United States government

NM_000335.5(SCN5A):c.3947T>G (p.Phe1316Cys) AND Cardiac arrhythmia

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Nov 20, 2023
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV001841858.13

Allele description [Variation Report for NM_000335.5(SCN5A):c.3947T>G (p.Phe1316Cys)]

NM_000335.5(SCN5A):c.3947T>G (p.Phe1316Cys)

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.3947T>G (p.Phe1316Cys)
Other names:
p.Phe1317Cys
HGVS:
  • NC_000003.12:g.38562428A>C
  • NG_008934.1:g.92245T>G
  • NM_000335.5:c.3947T>GMANE SELECT
  • NM_001099404.2:c.3950T>G
  • NM_001099405.2:c.3950T>G
  • NM_001160160.2:c.3947T>G
  • NM_001160161.2:c.3788T>G
  • NM_001354701.2:c.3947T>G
  • NM_198056.3:c.3950T>G
  • NP_000326.2:p.Phe1316Cys
  • NP_001092874.1:p.Phe1317Cys
  • NP_001092875.1:p.Phe1317Cys
  • NP_001153632.1:p.Phe1316Cys
  • NP_001153633.1:p.Phe1263Cys
  • NP_001341630.1:p.Phe1316Cys
  • NP_932173.1:p.Phe1317Cys
  • NP_932173.1:p.Phe1317Cys
  • LRG_289t1:c.3950T>G
  • LRG_289:g.92245T>G
  • LRG_289p1:p.Phe1317Cys
  • NC_000003.11:g.38603919A>C
  • NM_198056.2:c.3950T>G
Protein change:
F1263C
Links:
dbSNP: rs762546813
NCBI 1000 Genomes Browser:
rs762546813
Molecular consequence:
  • NM_000335.5:c.3947T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099404.2:c.3950T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099405.2:c.3950T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001160160.2:c.3947T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001160161.2:c.3788T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354701.2:c.3947T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198056.3:c.3950T>G - missense variant - [Sequence Ontology: SO:0001583]
Observations:
3

Condition(s)

Name:
Cardiac arrhythmia
Synonyms:
Cardiac rhythm disease
Identifiers:
EFO: EFO_0004269; MONDO: MONDO:0007263; MedGen: C0003811; Human Phenotype Ontology: HP:0011675

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001348728Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Dec 2, 2022) 		germlineclinical testing

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

SCV004821538All of Us Research Program, National Institutes of Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain Significance
(Nov 20, 2023) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown3not providednot provided108544not providedclinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV001348728.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This missense variant replaces phenylalanine with cysteine at codon 1317 of the SCN5A protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 2/272746 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From All of Us Research Program, National Institutes of Health, SCV004821538.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided3not providednot providedclinical testing PubMed (1)

Description

This missense variant replaces phenylalanine with cysteine at codon 1317 of the SCN5A protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 2/272746 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown108544not providednot provided3not providednot providednot provided

Last Updated: Nov 3, 2024