NM_000335.5(SCN5A):c.3944G>A (p.Arg1315Gln) AND Cardiac arrhythmia

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Jan 11, 2024
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:
RCV001841983.12

Allele description [Variation Report for NM_000335.5(SCN5A):c.3944G>A (p.Arg1315Gln)]

NM_000335.5(SCN5A):c.3944G>A (p.Arg1315Gln)

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.3944G>A (p.Arg1315Gln)
HGVS:
  • NC_000003.12:g.38562431C>T
  • NG_008934.1:g.92242G>A
  • NM_000335.5:c.3944G>AMANE SELECT
  • NM_001099404.2:c.3947G>A
  • NM_001099405.2:c.3947G>A
  • NM_001160160.2:c.3944G>A
  • NM_001160161.2:c.3785G>A
  • NM_001354701.2:c.3944G>A
  • NM_198056.3:c.3947G>A
  • NP_000326.2:p.Arg1315Gln
  • NP_001092874.1:p.Arg1316Gln
  • NP_001092875.1:p.Arg1316Gln
  • NP_001153632.1:p.Arg1315Gln
  • NP_001153633.1:p.Arg1262Gln
  • NP_001341630.1:p.Arg1315Gln
  • NP_932173.1:p.Arg1316Gln
  • NP_932173.1:p.Arg1316Gln
  • LRG_289t1:c.3947G>A
  • LRG_289:g.92242G>A
  • LRG_289p1:p.Arg1316Gln
  • NC_000003.11:g.38603922C>T
  • NM_198056.2:c.3947G>A
Protein change:
R1262Q
Links:
dbSNP: rs765907469
NCBI 1000 Genomes Browser:
rs765907469
Molecular consequence:
  • NM_000335.5:c.3944G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099404.2:c.3947G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099405.2:c.3947G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001160160.2:c.3944G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001160161.2:c.3785G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354701.2:c.3944G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198056.3:c.3947G>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
8

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
SCV001734203Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Sep 15, 2023) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

SCV004826957All of Us Research Program, National Institutes of Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain Significance
(Jan 11, 2024) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown8not providednot provided108544not providedclinical testing

Citations

PubMed

Clinical presentation and follow-up of women affected by Brugada syndrome.

Berthome P, Tixier R, Briand J, Geoffroy O, Babuty D, Mansourati J, Jesel L, Dupuis JM, Bru P, Kyndt F, Guyomarch B, Thollet A, Behar N, Mabo P, Sacher F, Probst V, Gourraud JB.

Heart Rhythm. 2019 Feb;16(2):260-267. doi: 10.1016/j.hrthm.2018.08.032. Epub 2018 Sep 5.

PubMed [citation]
PMID:
30193851

Post-mortem genetic investigation of cardiac disease-associated genes in sudden infant death syndrome (SIDS) cases.

Köffer J, Scheiper-Welling S, Verhoff MA, Bajanowski T, Kauferstein S.

Int J Legal Med. 2021 Jan;135(1):207-212. doi: 10.1007/s00414-020-02394-x. Epub 2020 Aug 12.

PubMed [citation]
PMID:
32789579
PMCID:
PMC7782403
See all PubMed Citations (4)

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV001734203.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This missense variant replaces arginine with glutamine at codon 1316 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). This variant is found within a highly conserved transmembrane domain (a.a. 1207-1466). Rare non-truncating variants in this region have been shown to be significantly overrepresented in individuals with long QT syndrome (PMID: 32893267). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with sudden infant death syndrome (PMID: 32789579) and in an individual with Brugada syndrome (PMID: 30193851). This variant has been identified in 7/273056 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, SCV004826957.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided8not providednot providedclinical testing PubMed (4)

Description

This missense variant replaces arginine with glutamine at codon 1316 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). This variant is found within a highly conserved transmembrane domain (a.a. 1207-1466). Rare non-truncating variants in this region have been shown to be significantly overrepresented in individuals with long QT syndrome (PMID: 32893267). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with sudden infant death syndrome (PMID: 32789579) and in an individual with Brugada syndrome (PMID: 30193851). This variant has been identified in 7/273056 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 provided8not providednot providednot provided

Last Updated: May 1, 2024