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NM_000335.5(SCN5A):c.3908C>T (p.Thr1303Met) AND Cardiac arrhythmia

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Dec 4, 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:
RCV001842354.11

Allele description [Variation Report for NM_000335.5(SCN5A):c.3908C>T (p.Thr1303Met)]

NM_000335.5(SCN5A):c.3908C>T (p.Thr1303Met)

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.3908C>T (p.Thr1303Met)
Other names:
p.T1304M:ACG>ATG
HGVS:
  • NC_000003.12:g.38562467G>A
  • NG_008934.1:g.92206C>T
  • NM_000335.5:c.3908C>TMANE SELECT
  • NM_001099404.2:c.3911C>T
  • NM_001099405.2:c.3911C>T
  • NM_001160160.2:c.3908C>T
  • NM_001160161.2:c.3749C>T
  • NM_001354701.2:c.3908C>T
  • NM_198056.3:c.3911C>T
  • NP_000326.2:p.Thr1303Met
  • NP_000326.2:p.Thr1303Met
  • NP_001092874.1:p.Thr1304Met
  • NP_001092874.1:p.Thr1304Met
  • NP_001092875.1:p.Thr1304Met
  • NP_001153632.1:p.Thr1303Met
  • NP_001153633.1:p.Thr1250Met
  • NP_001341630.1:p.Thr1303Met
  • NP_932173.1:p.Thr1304Met
  • NP_932173.1:p.Thr1304Met
  • LRG_289t1:c.3911C>T
  • LRG_289t2:c.3908C>T
  • LRG_289t3:c.3911C>T
  • LRG_289:g.92206C>T
  • LRG_289p1:p.Thr1304Met
  • LRG_289p2:p.Thr1303Met
  • LRG_289p3:p.Thr1304Met
  • NC_000003.11:g.38603958G>A
  • NM_000335.4:c.3908C>T
  • NM_001099404.1:c.3911C>T
  • NM_198056.2:c.3911C>T
Protein change:
T1250M
Links:
dbSNP: rs199473603
NCBI 1000 Genomes Browser:
rs199473603
Molecular consequence:
  • NM_000335.5:c.3908C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099404.2:c.3911C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099405.2:c.3911C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001160160.2:c.3908C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001160161.2:c.3749C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354701.2:c.3908C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198056.3:c.3911C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000913703Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Dec 4, 2023) 		germlineclinical testing

PubMed (12)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Sodium channel abnormalities are infrequent in patients with long QT syndrome: identification of two novel SCN5A mutations.

Wattanasirichaigoon D, Vesely MR, Duggal P, Levine JC, Blume ED, Wolff GS, Edwards SB, Beggs AH.

Am J Med Genet. 1999 Oct 29;86(5):470-6.

PubMed [citation]
PMID:
10508990

Prevalence of long-QT syndrome gene variants in sudden infant death syndrome.

Arnestad M, Crotti L, Rognum TO, Insolia R, Pedrazzini M, Ferrandi C, Vege A, Wang DW, Rhodes TE, George AL Jr, Schwartz PJ.

Circulation. 2007 Jan 23;115(3):361-7. Epub 2007 Jan 8.

PubMed [citation]
PMID:
17210839
See all PubMed Citations (12)

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV000913703.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (12)

Description

This missense variant replaces threonine with methionine at codon 1304 of the SCN5A protein. Computational prediction tools indicate that this variant has a deleterious impact on protein structure and function. Functional studies have shown inconsistent results regarding the impact of this variant on the SCN5A ion channel function (PMID: 17210841, 18451998). This variant has been reported in individuals affected with long QT syndrome (PMID: 19841300), early-onset lone atrial fibrillation (PMID: 22685113, 24144883), sudden unexplained death (PMID: 17210839, 17210841, 24631775, 32652122), and dilated cardiomyopathy (PMID: 36129056). This variant has been reported to segregate with long QT syndrome in multiple members of a family (PMID: 10508990). This variant has been reported in a small family with Brugada syndrome (PMID: 25210526). This variant has also been identified in 46/279030 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Due to the conflicting functional study results and appreciable allele frequency in the general population, the role of this variant in disease cannot be determined 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

Last Updated: Jun 2, 2024