Submissions for variant NM_001005242.3(PKP2):c.2062C>T (p.Gln688Ter)

dbSNP: rs1956192035

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001041240	SCV001204842	pathogenic	Arrhythmogenic right ventricular dysplasia 9	2020-04-26	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in PKP2 are known to be pathogenic (PMID: 15489853, 23911551). This variant has been observed in an individual affected with arrhythmogenic right ventricular cardiomyopathy (PMID: 26887364). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Gln732*) in the PKP2 gene. It is expected to result in an absent or disrupted protein product.
Color Diagnostics, LLC DBA Color Health	RCV001177243	SCV001341418	pathogenic	Cardiomyopathy	2019-10-14	criteria provided, single submitter	clinical testing	This variant changes 1 nucleotide in exon 11 of the PKP2 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has been reported in an individual affected with arrhythmogenic right ventricular cardiomyopathy (PMID: 26887364). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of PKP2 function is a known mechanism of disease. Based on the available evidence, this variant is classified as Pathogenic.