ClinVar Miner

Submissions for variant NM_001005242.3(PKP2):c.484A>G (p.Thr162Ala)

gnomAD frequency: 0.00001  dbSNP: rs765195368
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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 RCV001183497 SCV001349244 uncertain significance Cardiomyopathy 2023-03-07 criteria provided, single submitter clinical testing This missense variant replaces threonine with alanine at codon 162 of the PKP2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with PKP2-related disorders in the literature. This variant has been identified in 7/282760 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
GeneDx RCV001773431 SCV002003007 uncertain significance not provided 2020-02-10 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function
Invitae RCV001876101 SCV002127106 uncertain significance Arrhythmogenic right ventricular dysplasia 9 2023-08-10 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The alanine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 923064). This variant has not been reported in the literature in individuals affected with PKP2-related conditions. This variant is present in population databases (rs765195368, gnomAD 0.006%). This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 162 of the PKP2 protein (p.Thr162Ala).
Ambry Genetics RCV002339461 SCV002639438 likely benign Cardiovascular phenotype 2022-01-27 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: 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.
Fulgent Genetics, Fulgent Genetics RCV001876101 SCV002784456 uncertain significance Arrhythmogenic right ventricular dysplasia 9 2021-11-17 criteria provided, single submitter clinical testing

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