Submissions for variant NM_001005242.3(PKP2):c.986_992del (p.Ser329fs)

dbSNP: rs1373300155

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000627574	SCV000748574	likely pathogenic	not provided	2018-04-02	criteria provided, single submitter	clinical testing	The c.986_992delGTGGGAA variant in the PKP2 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.986_992delGTGGGAA variant causes a frameshift starting with codon Serine 329, changes this amino acid to an Isoleucine residue, and creates a premature Stop codon at position 21 of the new reading frame, denoted p.Ser329IlefsX21. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.986_992delGTGGGAA variant is not observed in large population cohorts (Lek et al., 2016). We interpret c.986_992delGTGGGAA as a likely pathogenic variant.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002529810	SCV003201623	pathogenic	Arrhythmogenic right ventricular dysplasia 9	2023-03-13	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Ser329Ilefs*21) 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 variant has not been reported in the literature in individuals affected with PKP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 524078). For these reasons, this variant has been classified as Pathogenic.