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NM_000335.5(SCN5A):c.44G>C (p.Arg15Thr) 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:
RCV001842478.13

Allele description [Variation Report for NM_000335.5(SCN5A):c.44G>C (p.Arg15Thr)]

NM_000335.5(SCN5A):c.44G>C (p.Arg15Thr)

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.44G>C (p.Arg15Thr)
HGVS:
  • NC_000003.12:g.38633264C>G
  • NG_008934.1:g.21409G>C
  • NM_000335.5:c.44G>CMANE SELECT
  • NM_001099404.2:c.44G>C
  • NM_001099405.2:c.44G>C
  • NM_001160160.2:c.44G>C
  • NM_001160161.2:c.44G>C
  • NM_001354701.2:c.44G>C
  • NM_198056.3:c.44G>C
  • NP_000326.2:p.Arg15Thr
  • NP_001092874.1:p.Arg15Thr
  • NP_001092875.1:p.Arg15Thr
  • NP_001153632.1:p.Arg15Thr
  • NP_001153633.1:p.Arg15Thr
  • NP_001341630.1:p.Arg15Thr
  • NP_932173.1:p.Arg15Thr
  • NP_932173.1:p.Arg15Thr
  • LRG_289t1:c.44G>C
  • LRG_289:g.21409G>C
  • LRG_289p1:p.Arg15Thr
  • NC_000003.11:g.38674755C>G
  • NM_198056.2:c.44G>C
Protein change:
R15T
Links:
dbSNP: rs373410109
NCBI 1000 Genomes Browser:
rs373410109
Molecular consequence:
  • NM_000335.5:c.44G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099404.2:c.44G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099405.2:c.44G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001160160.2:c.44G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001160161.2:c.44G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354701.2:c.44G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198056.3:c.44G>C - missense variant - [Sequence Ontology: SO:0001583]
Observations:
11

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
SCV000914098Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Dec 6, 2022) 		germlineclinical testing

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

SCV004824241All of Us Research Program, National Institutes of Health
criteria provided, single submitter

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

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown11not providednot provided108544not providedclinical testing

Citations

PubMed

Identification and characterization of a novel recessive KCNQ1 mutation associated with Romano-Ward Long-QT syndrome in two Iranian families.

Zafari Z, Dalili M, Zeinali S, Saber S, Fazeli Far AF, Akbari MT.

J Electrocardiol. 2017 Nov - Dec;50(6):912-918. doi: 10.1016/j.jelectrocard.2017.07.012. Epub 2017 Jul 12.

PubMed [citation]
PMID:
29033053

Variant panorama in 1,385 index patients and sensitivity of expanded next-generation sequencing panels in arrhythmogenic disorders.

Marschall C, Moscu-Gregor A, Klein HG.

Cardiovasc Diagn Ther. 2019 Oct;9(Suppl 2):S292-S298. doi: 10.21037/cdt.2019.06.06.

PubMed [citation]
PMID:
31737537
PMCID:
PMC6837920
See all PubMed Citations (3)

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV000914098.4

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

Description

This missense variant replaces arginine with threonine at codon 15 of the SCN5A protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in two individuals affected with long QT syndrome, in an individual suspected of having long QT syndrome, and in five asymptomatic family members (PMID: 29033053, 31737537). This variant has been identified in 11/279748 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, SCV004824241.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided11not providednot providedclinical testing PubMed (3)

Description

This missense variant replaces arginine with threonine at codon 15 of the SCN5A protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in two individuals affected with long QT syndrome, in an individual suspected of having long QT syndrome, and in five asymptomatic family members (PMID: 29033053, 31737537). This variant has been identified in 11/279748 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 provided11not providednot providednot provided

Last Updated: Oct 26, 2024