ClinVar Miner

Submissions for variant NM_001005242.3(PKP2):c.1177C>T (p.Gln393Ter)

dbSNP: rs786204393
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001389963 SCV001591525 pathogenic Arrhythmogenic right ventricular dysplasia 9 2023-12-15 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln393*) in the PKP2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PKP2 are known to be pathogenic (PMID: 15489853, 23911551). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with clinical features of arrhythmogenic right ventricular cardiomyopathy (PMID: 23812740, 27532257). ClinVar contains an entry for this variant (Variation ID: 188658). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV001778768 SCV002015761 likely pathogenic not provided 2021-11-05 criteria provided, single submitter clinical testing Reported in association with arrhythmogenic right ventricular cardiomyopathy (ARVC) (Baskin et al., 2013; Walsh et al., 2017); Not observed at significant frequency in large population cohorts (Lek et al., 2016); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 27532257, 23812740, 31402444, 26582918)
Ambry Genetics RCV002326930 SCV002637582 pathogenic Cardiovascular phenotype 2019-08-30 criteria provided, single submitter clinical testing The p.Q393* pathogenic mutation (also known as c.1177C>T), located in coding exon 5 of the PKP2 gene, results from a C to T substitution at nucleotide position 1177. This changes the amino acid from a glutamine to a stop codon within coding exon 5. This alteration has been reported in association with arrhythmogenic right ventricular cardiomyopathy (ARVC) (Baskin B et al. Hum. Genet., 2013 Nov;132:1245-52; Walsh R et al. Genet. Med., 2017 02;19:192-203). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

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