Submissions for variant NM_001005242.3(PKP2):c.962_965del (p.Val321fs)

dbSNP: rs2137946218

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Petrovsky National Research Centre of Surgery, The Federal Agency for Scientific Organizations	RCV001838972	SCV002098399	likely pathogenic	Arrhythmogenic right ventricular dysplasia 9	2022-02-25	criteria provided, single submitter	clinical testing	This sequence change c.962_965del creates a premature translational stop signal (p.Val321Alafs*30) in the PKP2 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in databases (gnomAD, LOVD). This variant has been observed in an individual affected with arrhythmogenic right ventricular cardiomyopathy (ARVC). Loss-of-function variants in PKP2 are known to be pathogenic (PMID: 15489853, 23911551). For these reasons, this variant has been classified as Likely Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001838972	SCV004532600	pathogenic	Arrhythmogenic right ventricular dysplasia 9	2024-01-19	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Val321Alafs*30) 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, 17041889, 23911551). This variant is not present in population databases (gnomAD no frequency). 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: 1342294). For these reasons, this variant has been classified as Pathogenic.