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NM_000335.5(SCN5A):c.73G>A (p.Glu25Lys) AND Cardiac arrhythmia

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Feb 5, 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:
RCV001842526.13

Allele description [Variation Report for NM_000335.5(SCN5A):c.73G>A (p.Glu25Lys)]

NM_000335.5(SCN5A):c.73G>A (p.Glu25Lys)

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.73G>A (p.Glu25Lys)
HGVS:
  • NC_000003.12:g.38633235C>T
  • NG_008934.1:g.21438G>A
  • NM_000335.5:c.73G>AMANE SELECT
  • NM_001099404.2:c.73G>A
  • NM_001099405.2:c.73G>A
  • NM_001160160.2:c.73G>A
  • NM_001160161.2:c.73G>A
  • NM_001354701.2:c.73G>A
  • NM_198056.3:c.73G>A
  • NP_000326.2:p.Glu25Lys
  • NP_001092874.1:p.Glu25Lys
  • NP_001092875.1:p.Glu25Lys
  • NP_001153632.1:p.Glu25Lys
  • NP_001153633.1:p.Glu25Lys
  • NP_001341630.1:p.Glu25Lys
  • NP_932173.1:p.Glu25Lys
  • NP_932173.1:p.Glu25Lys
  • LRG_289t1:c.73G>A
  • LRG_289:g.21438G>A
  • LRG_289p1:p.Glu25Lys
  • NC_000003.11:g.38674726C>T
  • NM_198056.2:c.73G>A
Protein change:
E25K
Links:
dbSNP: rs747251132
NCBI 1000 Genomes Browser:
rs747251132
Molecular consequence:
  • NM_000335.5:c.73G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099404.2:c.73G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099405.2:c.73G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001160160.2:c.73G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001160161.2:c.73G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354701.2:c.73G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198056.3:c.73G>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
4

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
SCV001359189Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Aug 23, 2023) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV004828433All of Us Research Program, National Institutes of Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain Significance
(Feb 5, 2024) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown4not providednot provided108544not providedclinical testing

Citations

PubMed

Rare variants in genes encoding the cardiac sodium channel and associated compounds and their impact on outcome of catheter ablation of atrial fibrillation.

Husser D, Ueberham L, Hindricks G, Büttner P, Ingram C, Weeke P, Shoemaker MB, Adams V, Arya A, Sommer P, Darbar D, Roden DM, Bollmann A.

PLoS One. 2017;12(8):e0183690. doi: 10.1371/journal.pone.0183690.

PubMed [citation]
PMID:
28837624
PMCID:
PMC5570360

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV001359189.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This missense variant replaces glutamic acid with lysine at codon 25 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). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in 1 individual affected with atrial fibrillation (PMID: 28837624). This variant has been identified in 2/248816 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, SCV004828433.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided4not providednot providedclinical testing PubMed (2)

Description

This missense variant replaces glutamic acid with lysine at codon 25 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). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in 1 individual affected with atrial fibrillation (PMID: 28837624). This variant has been identified in 2/248816 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 provided4not providednot providednot provided

Last Updated: Nov 3, 2024