ClinVar Miner

Submissions for variant NM_001005242.3(PKP2):c.2072G>A (p.Arg691Gln)

gnomAD frequency: 0.00002  dbSNP: rs547215531
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001177065 SCV001341193 likely benign Cardiomyopathy 2020-01-14 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001232028 SCV001404571 uncertain significance Arrhythmogenic right ventricular dysplasia 9 2022-03-18 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 735 of the PKP2 protein (p.Arg735Gln). This variant is present in population databases (rs547215531, gnomAD 0.05%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with arrhythmogenic right-ventricular cardiomyopathy (PMID: 25825460). ClinVar contains an entry for this variant (Variation ID: 919115). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
GeneDx RCV001568839 SCV001792780 uncertain significance not provided 2020-09-10 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Reported in ClinVar (ClinVar Variant ID# 919115; Landrum et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 25825460)
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV001177065 SCV002043316 likely benign Cardiomyopathy 2021-05-28 criteria provided, single submitter clinical testing
Ambry Genetics RCV004033003 SCV005022657 likely benign Cardiovascular phenotype 2023-10-06 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

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