U.S. flag

An official website of the United States government

NM_000335.5(SCN5A):c.2677C>T (p.Arg893Cys) AND not provided

Germline classification:
Conflicting interpretations of pathogenicity (3 submissions)
Last evaluated:
Mar 28, 2024
Review status:
criteria provided, conflicting classifications
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:
RCV000183009.7

Allele description [Variation Report for NM_000335.5(SCN5A):c.2677C>T (p.Arg893Cys)]

NM_000335.5(SCN5A):c.2677C>T (p.Arg893Cys)

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.2677C>T (p.Arg893Cys)
Other names:
p.R893C:CGC>TGC
HGVS:
  • NC_000003.12:g.38585801G>A
  • NG_008934.1:g.68872C>T
  • NM_000335.5:c.2677C>TMANE SELECT
  • NM_001099404.2:c.2677C>T
  • NM_001099405.2:c.2677C>T
  • NM_001160160.2:c.2677C>T
  • NM_001160161.2:c.2677C>T
  • NM_001354701.2:c.2677C>T
  • NM_198056.3:c.2677C>T
  • NP_000326.2:p.Arg893Cys
  • NP_000326.2:p.Arg893Cys
  • NP_001092874.1:p.Arg893Cys
  • NP_001092875.1:p.Arg893Cys
  • NP_001153632.1:p.Arg893Cys
  • NP_001153633.1:p.Arg893Cys
  • NP_001341630.1:p.Arg893Cys
  • NP_932173.1:p.Arg893Cys
  • NP_932173.1:p.Arg893Cys
  • LRG_289t1:c.2677C>T
  • LRG_289t2:c.2677C>T
  • LRG_289:g.68872C>T
  • LRG_289p1:p.Arg893Cys
  • LRG_289p2:p.Arg893Cys
  • NC_000003.11:g.38627292G>A
  • NM_000335.4:c.2677C>T
  • NM_198056.2:c.2677C>T
  • Q14524:p.Arg893Cys
Protein change:
R893C
Links:
UniProtKB: Q14524#VAR_074390; dbSNP: rs199473171
NCBI 1000 Genomes Browser:
rs199473171
Molecular consequence:
  • NM_000335.5:c.2677C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099404.2:c.2677C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099405.2:c.2677C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001160160.2:c.2677C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001160161.2:c.2677C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354701.2:c.2677C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198056.3:c.2677C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000235415GeneDx
criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)
Uncertain significance
(Feb 1, 2024)
germlineclinical testing

Citation Link,

SCV000953030Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Jan 29, 2024)
germlineclinical testing

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

SCV005198169Clinical Genetics Laboratory, Skane University Hospital Lund
criteria provided, single submitter

(ACMG Guidelines, 2015)
Likely pathogenic
(Mar 28, 2024)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Copy number variations of SCN5A in Brugada syndrome.

Sonoda K, Ohno S, Ozawa J, Hayano M, Hattori T, Kobori A, Yahata M, Aburadani I, Watanabe S, Matsumoto Y, Makiyama T, Horie M.

Heart Rhythm. 2018 Aug;15(8):1179-1188. doi: 10.1016/j.hrthm.2018.03.033. Epub 2018 Mar 21.

PubMed [citation]
PMID:
29574140

[Clinic and genetic polymorphism of Brugada syndrome in Russian patients, caused by mutation in SCN5A gene].

Zakliaz'minskaia EV, Shestak AG, Revishvili ASh, Pronicheva IV, Podoliak DG, Nechaenko MA, Poliakov AV, Dzemeshkevich SL.

Khirurgiia (Mosk). 2013;(2):49-53. Russian.

PubMed [citation]
PMID:
23503384
See all PubMed Citations (5)

Details of each submission

From GeneDx, SCV000235415.16

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Not observed at significant frequency in large population cohorts (gnomAD); Published functional studies are equivocal regarding whether this variant has a damaging effect (PMID: 35305865, 34219138); This variant is associated with the following publications: (PMID: 22581653, 24136861, 28341781, 28150151, 30371189, 30662450, 35305865, 34219138, 35617207, 31737537, 30203441, 30193851, 20129283, 29574140, 35331424)

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV000953030.5

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

Description

This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 893 of the SCN5A protein (p.Arg893Cys). This variant is present in population databases (rs199473171, gnomAD 0.004%). This missense change has been observed in individuals with Brugada syndrome (PMID: 28341781, 29574140; Invitae). ClinVar contains an entry for this variant (Variation ID: 67748). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. This variant disrupts the p.Arg893 amino acid residue in SCN5A. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 23503384, 28341781; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Clinical Genetics Laboratory, Skane University Hospital Lund, SCV005198169.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 16, 2024