NM_000335.5(SCN5A):c.4490T>C (p.Met1497Thr) AND Cardiovascular phenotype

Clinical significance:Likely pathogenic (Last evaluated: Jun 10, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000619022.1

Allele description [Variation Report for NM_000335.5(SCN5A):c.4490T>C (p.Met1497Thr)]

NM_000335.5(SCN5A):c.4490T>C (p.Met1497Thr)

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.4490T>C (p.Met1497Thr)
Other names:
p.M1498T:ATG>ACG
HGVS:
  • NC_000003.12:g.38555705A>G
  • NG_008934.1:g.98968T>C
  • NM_000335.5:c.4490T>CMANE SELECT
  • NM_001099404.2:c.4493T>C
  • NM_001099405.2:c.4439T>C
  • NM_001160160.2:c.4490T>C
  • NM_001160161.2:c.4331T>C
  • NM_001354701.2:c.4436T>C
  • NM_198056.2:c.4493T>C
  • NM_198056.3:c.4493T>C
  • NP_000326.2:p.Met1497Thr
  • NP_001092874.1:p.Met1498Thr
  • NP_001092875.1:p.Met1480Thr
  • NP_001153632.1:p.Met1497Thr
  • NP_001153633.1:p.Met1444Thr
  • NP_001341630.1:p.Met1479Thr
  • NP_932173.1:p.Met1498Thr
  • NP_932173.1:p.Met1498Thr
  • LRG_289t1:c.4493T>C
  • LRG_289:g.98968T>C
  • LRG_289p1:p.Met1498Thr
  • NC_000003.11:g.38597196A>G
  • Q14524:p.Met1498Thr
Protein change:
M1444T
Links:
UniProtKB: Q14524#VAR_074744; dbSNP: rs199473263
NCBI 1000 Genomes Browser:
rs199473263
Molecular consequence:
  • NM_000335.5:c.4490T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099404.2:c.4493T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099405.2:c.4439T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001160160.2:c.4490T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001160161.2:c.4331T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354701.2:c.4436T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198056.2:c.4493T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198056.3:c.4493T>C - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Name:
Cardiovascular phenotype
Identifiers:
MedGen: CN230736

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000737387Ambry Geneticscriteria provided, single submitter
Likely pathogenic
(Jun 10, 2019)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not providedclinical testing

Citations

PubMed

Genetic testing in the long QT syndrome: development and validation of an efficient approach to genotyping in clinical practice.

Napolitano C, Priori SG, Schwartz PJ, Bloise R, Ronchetti E, Nastoli J, Bottelli G, Cerrone M, Leonardi S.

JAMA. 2005 Dec 21;294(23):2975-80.

PubMed [citation]
PMID:
16414944

Spectrum and prevalence of mutations from the first 2,500 consecutive unrelated patients referred for the FAMILION long QT syndrome genetic test.

Kapplinger JD, Tester DJ, Salisbury BA, Carr JL, Harris-Kerr C, Pollevick GD, Wilde AA, Ackerman MJ.

Heart Rhythm. 2009 Sep;6(9):1297-303. doi: 10.1016/j.hrthm.2009.05.021. Epub 2009 Jun 23.

PubMed [citation]
PMID:
19716085
PMCID:
PMC3049907
See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV000737387.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (3)

Description

The p.M1498T variant (also known as c.4493T>C), located in coding exon 25 of the SCN5A gene, results from a T to C substitution at nucleotide position 4493. The methionine at codon 1498 is replaced by threonine, an amino acid with similar properties located in the cytoplasmic region linking transmembrane protein domains III and IV. This variant was previously described in a patient with long QT syndrome (Napolitano C et al. JAMA. 2005;294(23):2975-80). Additionally, other alterations involving the same amino acid position (p.M1498V c.4492A>G; p.M198R c.4493T>G) have been observed either in a patient from a study of long QT syndrome clinical genetic testing or in a family with sick sinus syndrome (Kapplinger JD et al. Heart Rhythm. 2009;6(9):1297-303; Asadi M et al. Anatol J Cardiol, 2016 Mar;16:170-4). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown1not providednot provided1not providednot providednot provided

Last Updated: Oct 30, 2021

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