NM_181703.4(GJA5):c.525C>G (p.Tyr175Ter) AND multiple conditions

Clinical significance:Uncertain significance (Last evaluated: Aug 19, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001337728.1

Allele description [Variation Report for NM_181703.4(GJA5):c.525C>G (p.Tyr175Ter)]

NM_181703.4(GJA5):c.525C>G (p.Tyr175Ter)

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.525C>G (p.Tyr175Ter)
HGVS:
  • NC_000001.11:g.147758714G>C
  • NG_009369.2:g.19661C>G
  • NM_005266.7:c.525C>G
  • NM_181703.4:c.525C>GMANE SELECT
  • NP_005257.2:p.Tyr175Ter
  • NP_859054.1:p.Tyr175Ter
  • NC_000001.10:g.147230822G>C
Protein change:
Y175*
Molecular consequence:
  • NM_005266.7:c.525C>G - nonsense - [Sequence Ontology: SO:0001587]
  • NM_181703.4:c.525C>G - nonsense - [Sequence Ontology: SO:0001587]

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
SCV001531340Invitaecriteria provided, single submitter
Uncertain significance
(Aug 19, 2020)
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, SCV001531340.1

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

Description

This sequence change results in a premature translational stop signal in the GJA5 gene (p.Tyr175*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 184 amino acids of the GJA5 protein. 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 conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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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