ClinVar Miner

Submissions for variant NM_001005242.3(PKP2):c.934T>G (p.Ser312Ala)

gnomAD frequency: 0.00001  dbSNP: rs756604557
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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 RCV001180152 SCV001345020 likely benign Cardiomyopathy 2018-12-13 criteria provided, single submitter clinical testing
GeneDx RCV001586025 SCV001819690 uncertain significance not provided 2019-10-17 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function
Invitae RCV001875973 SCV002191498 uncertain significance Arrhythmogenic right ventricular dysplasia 9 2023-10-17 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 312 of the PKP2 protein (p.Ser312Ala). This variant is present in population databases (rs756604557, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with PKP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 921011). 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. 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002271626 SCV002555928 uncertain significance not specified 2022-06-16 criteria provided, single submitter clinical testing
Ambry Genetics RCV003163411 SCV003866262 uncertain significance Cardiovascular phenotype 2023-01-12 criteria provided, single submitter clinical testing The p.S312A variant (also known as c.934T>G), located in coding exon 3 of the PKP2 gene, results from a T to G substitution at nucleotide position 934. The serine at codon 312 is replaced by alanine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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