NM_000335.5(SCN5A):c.1705C>G (p.Arg569Gly) AND not provided

Clinical significance:Uncertain significance (Last evaluated: Dec 20, 2016)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000183172.2

Allele description [Variation Report for NM_000335.5(SCN5A):c.1705C>G (p.Arg569Gly)]

NM_000335.5(SCN5A):c.1705C>G (p.Arg569Gly)

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.1705C>G (p.Arg569Gly)
Other names:
p.R569G:CGG>GGG
HGVS:
  • NC_000003.12:g.38603897G>C
  • NG_008934.1:g.50776C>G
  • NM_000335.5:c.1705C>GMANE SELECT
  • NM_001099404.2:c.1705C>G
  • NM_001099405.1:c.1705C>G
  • NM_001099405.2:c.1705C>G
  • NM_001160160.2:c.1705C>G
  • NM_001160161.2:c.1705C>G
  • NM_001354701.2:c.1705C>G
  • NM_198056.2:c.1705C>G
  • NM_198056.3:c.1705C>G
  • NP_000326.2:p.Arg569Gly
  • NP_001092874.1:p.Arg569Gly
  • NP_001092875.1:p.Arg569Gly
  • NP_001092875.1:p.Arg569Gly
  • NP_001153632.1:p.Arg569Gly
  • NP_001153633.1:p.Arg569Gly
  • NP_001341630.1:p.Arg569Gly
  • NP_932173.1:p.Arg569Gly
  • NP_932173.1:p.Arg569Gly
  • LRG_289t1:c.1705C>G
  • LRG_289:g.50776C>G
  • LRG_289p1:p.Arg569Gly
  • NC_000003.11:g.38645388G>C
Protein change:
R569G
Links:
dbSNP: rs199473576
NCBI 1000 Genomes Browser:
rs199473576
Molecular consequence:
  • NM_000335.5:c.1705C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099404.2:c.1705C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099405.1:c.1705C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099405.2:c.1705C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001160160.2:c.1705C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001160161.2:c.1705C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354701.2:c.1705C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198056.2:c.1705C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198056.3:c.1705C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000235589GeneDxcriteria provided, single submitter
Uncertain significance
(Dec 20, 2016)
germlineclinical testing

Citation Link

Summary from all submissions

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

Details of each submission

From GeneDx, SCV000235589.10

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

Description

A variant of uncertain significance has been identified in the SCN5A gene. The R569G variant has been published in one patient referred for LQTS testing (Kapplinger et al., 2015); however, additional clinical information was not provided. Additionally, functional studies by Kapplinger et al. (2015) suggest a deleterious effect of this variant, but additional studies are needed to validate the functional effect of this variant. A missense variant at the same residue (R569W) has been reported in the Human Gene Mutation Database (Stenson et al., 2014), however, the pathogencity of this variant has not been definitively determined. Nevertheless, the R569G variant was not observed in approximately 6,200 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R569G variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position where only amino acids with similar properties to Arginine are tolerated across species. Finally, in silico analysis predicts this variant is probably damaging to the protein structure/function.

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

Last Updated: Oct 25, 2021

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