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NM_000335.5(SCN5A):c.2071G>A (p.Ala691Thr) AND not provided

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Nov 27, 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:
RCV001811346.16

Allele description [Variation Report for NM_000335.5(SCN5A):c.2071G>A (p.Ala691Thr)]

NM_000335.5(SCN5A):c.2071G>A (p.Ala691Thr)

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.2071G>A (p.Ala691Thr)
HGVS:
  • NC_000003.12:g.38597920C>T
  • NG_008934.1:g.56753G>A
  • NM_000335.5:c.2071G>AMANE SELECT
  • NM_001099404.2:c.2071G>A
  • NM_001099405.2:c.2071G>A
  • NM_001160160.2:c.2071G>A
  • NM_001160161.2:c.2071G>A
  • NM_001354701.2:c.2071G>A
  • NM_198056.3:c.2071G>A
  • NP_000326.2:p.Ala691Thr
  • NP_001092874.1:p.Ala691Thr
  • NP_001092875.1:p.Ala691Thr
  • NP_001153632.1:p.Ala691Thr
  • NP_001153633.1:p.Ala691Thr
  • NP_001341630.1:p.Ala691Thr
  • NP_932173.1:p.Ala691Thr
  • NP_932173.1:p.Ala691Thr
  • LRG_289t1:c.2071G>A
  • LRG_289:g.56753G>A
  • LRG_289p1:p.Ala691Thr
  • NC_000003.11:g.38639411C>T
  • NM_198056.2:c.2071G>A
Protein change:
A691T
Links:
dbSNP: rs199473146
NCBI 1000 Genomes Browser:
rs199473146
Molecular consequence:
  • NM_000335.5:c.2071G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099404.2:c.2071G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099405.2:c.2071G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001160160.2:c.2071G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001160161.2:c.2071G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354701.2:c.2071G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198056.3:c.2071G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000760244Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Nov 27, 2023) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV002049778ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
criteria provided, single submitter

(ARUP Molecular Germline Variant Investigation Process 2021)		Uncertain significance
(Sep 8, 2021) 		germlineclinical testing

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Four potassium channel mutations account for 73% of the genetic spectrum underlying long-QT syndrome (LQTS) and provide evidence for a strong founder effect in Finland.

Fodstad H, Swan H, Laitinen P, Piippo K, Paavonen K, Viitasalo M, Toivonen L, Kontula K.

Ann Med. 2004;36 Suppl 1:53-63.

PubMed [citation]
PMID:
15176425

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV000760244.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 691 of the SCN5A protein (p.Ala691Thr). This variant is present in population databases (rs199473146, gnomAD 0.07%). This missense change has been observed in individual(s) with Long-QT syndrome (PMID: 15176425). ClinVar contains an entry for this variant (Variation ID: 67711). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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.

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

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV002049778.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 13, 2024