NM_181703.4(GJA5):c.411G>T (p.Glu137Asp) AND multiple conditions

Clinical significance:Uncertain significance (Last evaluated: Jul 24, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000799878.1

Allele description [Variation Report for NM_181703.4(GJA5):c.411G>T (p.Glu137Asp)]

NM_181703.4(GJA5):c.411G>T (p.Glu137Asp)

Gene:
GJA5:gap junction protein alpha 5 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1q21.2
Genomic location:
Preferred name:
NM_181703.4(GJA5):c.411G>T (p.Glu137Asp)
HGVS:
  • NC_000001.11:g.147758828C>A
  • NG_009369.2:g.19547G>T
  • NM_005266.6:c.411G>T
  • NM_181703.4:c.411G>TMANE SELECT
  • NP_005257.2:p.Glu137Asp
  • NP_859054.1:p.Glu137Asp
  • NC_000001.10:g.147230936C>A
Protein change:
E137D
Links:
dbSNP: rs200288659
NCBI 1000 Genomes Browser:
rs200288659
Molecular consequence:
  • NM_005266.6:c.411G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181703.4:c.411G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Atrial standstill 1 (ATRST1)
Synonyms:
ATRIAL CARDIOMYOPATHY WITH HEART BLOCK; CARDIOMYOPATHY, FAMILIAL, WITH CONDUCTION DISTURBANCE
Identifiers:
MONDO: MONDO:0007171; MedGen: C4551959; Orphanet: 1344; OMIM: 108770
Name:
Atrial fibrillation, familial, 11 (ATFB11)
Identifiers:
MONDO: MONDO:0013544; MedGen: C3279693; OMIM: 614049

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000939561Invitaecriteria provided, single submitter
Uncertain significance
(Jul 24, 2018)
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

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000939561.1

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

Description

This sequence change replaces glutamic acid with aspartic acid at codon 137 of the GJA5 protein (p.Glu137Asp). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and aspartic acid. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with GJA5-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Oct 7, 2021

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