ClinVar Miner

Submissions for variant NM_001005242.3(PKP2):c.1989G>T (p.Gln663His)

gnomAD frequency: 0.00001  dbSNP: rs765884775
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000484502 SCV000573844 uncertain significance not provided 2022-05-16 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV001319012 SCV001509736 uncertain significance Arrhythmogenic right ventricular dysplasia 9 2024-10-03 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 707 of the PKP2 protein (p.Gln707His). This variant is present in population databases (rs765884775, gnomAD 0.0009%). 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: 424067). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.
Color Diagnostics, LLC DBA Color Health RCV001524970 SCV001734956 uncertain significance Cardiomyopathy 2020-11-02 criteria provided, single submitter clinical testing This missense variant replaces glutamine with histidine at codon 707 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 cardiovascular disorders in the literature. This variant has been identified in 1/251414 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.
Ambry Genetics RCV002420243 SCV002726048 uncertain significance Cardiovascular phenotype 2018-04-10 criteria provided, single submitter clinical testing The p.Q707H variant (also known as c.2121G>T), located in coding exon 10 of the PKP2 gene, results from a G to T substitution at nucleotide position 2121. The glutamine at codon 707 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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