U.S. flag

An official website of the United States government

NM_000335.5(SCN5A):c.316A>G (p.Ser106Gly) AND Cardiac arrhythmia

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Oct 30, 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:
RCV001842601.13

Allele description [Variation Report for NM_000335.5(SCN5A):c.316A>G (p.Ser106Gly)]

NM_000335.5(SCN5A):c.316A>G (p.Ser106Gly)

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.316A>G (p.Ser106Gly)
HGVS:
  • NC_000003.12:g.38630387T>C
  • NG_008934.1:g.24286A>G
  • NM_000335.5:c.316A>GMANE SELECT
  • NM_001099404.2:c.316A>G
  • NM_001099405.2:c.316A>G
  • NM_001160160.2:c.316A>G
  • NM_001160161.2:c.316A>G
  • NM_001354701.2:c.316A>G
  • NM_198056.3:c.316A>G
  • NP_000326.2:p.Ser106Gly
  • NP_001092874.1:p.Ser106Gly
  • NP_001092875.1:p.Ser106Gly
  • NP_001153632.1:p.Ser106Gly
  • NP_001153633.1:p.Ser106Gly
  • NP_001341630.1:p.Ser106Gly
  • NP_932173.1:p.Ser106Gly
  • NP_932173.1:p.Ser106Gly
  • LRG_289t1:c.316A>G
  • LRG_289:g.24286A>G
  • LRG_289p1:p.Ser106Gly
  • NC_000003.11:g.38671878T>C
  • NM_198056.2:c.316A>G
Protein change:
S106G
Links:
dbSNP: rs1331765859
NCBI 1000 Genomes Browser:
rs1331765859
Molecular consequence:
  • NM_000335.5:c.316A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099404.2:c.316A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099405.2:c.316A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001160160.2:c.316A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001160161.2:c.316A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354701.2:c.316A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198056.3:c.316A>G - missense variant - [Sequence Ontology: SO:0001583]
Observations:
3

Condition(s)

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001342394Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Mar 24, 2023) 		germlineclinical testing

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

SCV004822937All of Us Research Program, National Institutes of Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain Significance
(Oct 30, 2023) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown3not providednot provided108544not providedclinical testing

Citations

PubMed

Molecular autopsy of sudden unexplained deaths reveals genetic predispositions for cardiac diseases among young forensic cases.

Hellenthal N, Gaertner-Rommel A, Klauke B, Paluszkiewicz L, Stuhr M, Kerner T, Farr M, Püschel K, Milting H.

Europace. 2017 Nov 1;19(11):1881-1890. doi: 10.1093/europace/euw247.

PubMed [citation]
PMID:
29016939

Characterization of an N-terminal Na(v)1.5 channel variant - a potential risk factor for arrhythmias and sudden death?

Scheiper-Welling S, Zuccolini P, Rauh O, Beckmann BM, Geisen C, Moroni A, Thiel G, Kauferstein S.

BMC Med Genet. 2020 Nov 19;21(1):227. doi: 10.1186/s12881-020-01170-3.

PubMed [citation]
PMID:
33213388
PMCID:
PMC7678220
See all PubMed Citations (3)

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV001342394.3

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

Description

This missense variant replaces serine with glycine at codon 106 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). A functional study has shown that this variant causes an increase in sodium channel current density and affects voltage-dependent activation and inactivation in transfected HEK293 cells (PMID: 33213388). This variant has been reported in two individuals affected with sudden unexplained death or survived cardiac arrest, who showed no ECG abnormalities (PMID: 29016939, 33213388). This variant has not been identified 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, SCV004822937.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided3not providednot providedclinical testing PubMed (3)

Description

This missense variant replaces serine with glycine at codon 106 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). A functional study has shown that this variant causes an increase in sodium channel current density and affects voltage-dependent activation and inactivation in transfected HEK293 cells (PMID: 33213388). This variant has been reported in two individuals affected with sudden unexplained death or survived cardiac arrest, who showed no ECG abnormalities (PMID: 29016939, 33213388). This variant has not been identified 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 provided3not providednot providednot provided

Last Updated: Oct 13, 2024