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NM_000335.5(SCN5A):c.4799T>A (p.Leu1600His) AND Cardiac arrhythmia

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Dec 13, 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:
RCV003591970.3

Allele description [Variation Report for NM_000335.5(SCN5A):c.4799T>A (p.Leu1600His)]

NM_000335.5(SCN5A):c.4799T>A (p.Leu1600His)

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.4799T>A (p.Leu1600His)
HGVS:
  • NC_000003.12:g.38554290A>T
  • NG_008934.1:g.100383T>A
  • NM_000335.5:c.4799T>AMANE SELECT
  • NM_001099404.2:c.4802T>A
  • NM_001099405.2:c.4748T>A
  • NM_001160160.2:c.4714+85T>A
  • NM_001160161.2:c.4640T>A
  • NM_001354701.2:c.4745T>A
  • NM_198056.3:c.4802T>A
  • NP_000326.2:p.Leu1600His
  • NP_000326.2:p.Leu1600His
  • NP_001092874.1:p.Leu1601His
  • NP_001092874.1:p.Leu1601His
  • NP_001092875.1:p.Leu1583His
  • NP_001153633.1:p.Leu1547His
  • NP_001341630.1:p.Leu1582His
  • NP_932173.1:p.Leu1601His
  • NP_932173.1:p.Leu1601His
  • LRG_289t1:c.4802T>A
  • LRG_289t2:c.4799T>A
  • LRG_289t3:c.4802T>A
  • LRG_289:g.100383T>A
  • LRG_289p1:p.Leu1601His
  • LRG_289p2:p.Leu1600His
  • LRG_289p3:p.Leu1601His
  • NC_000003.11:g.38595781A>T
  • NM_000335.4:c.4799T>A
  • NM_001099404.1:c.4802T>A
  • NM_198056.2:c.4802T>A
  • NM_198056.2:c.4802T>A
  • NR_176299.1:n.5548T>A
Protein change:
L1547H
Molecular consequence:
  • NM_001160160.2:c.4714+85T>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000335.5:c.4799T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099404.2:c.4802T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099405.2:c.4748T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001160161.2:c.4640T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354701.2:c.4745T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198056.3:c.4802T>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

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
SCV004361619Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

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

PubMed (1)
[See all records that cite this PMID]

SCV004841929All of Us Research Program, National Institutes of Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain Significance
(Dec 13, 2023) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided108544not providedclinical testing

Citations

PubMed

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, SCV004361619.1

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

Description

This missense variant replaces leucine with histidine at codon 1601 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 not been reported in individuals affected with SCN5A-related disorders in the literature. This variant has been identified in 2/247456 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, SCV004841929.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (1)

Description

This missense variant replaces leucine with histidine at codon 1601 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 not been reported in individuals affected with SCN5A-related disorders in the literature. This variant has been identified in 2/247456 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 provided1not providednot providednot provided

Last Updated: Jun 17, 2024