Submissions for variant NM_001005242.3(PKP2):c.94C>A (p.Leu32Met)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003508174	SCV004261160	uncertain significance	Arrhythmogenic right ventricular dysplasia 9	2024-06-11	criteria provided, single submitter	clinical testing	This sequence change replaces leucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 32 of the PKP2 protein (p.Leu32Met). 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. 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.
Clinical Genomics Laboratory, Stanford Medicine	RCV003508174	SCV005062015	uncertain significance	Arrhythmogenic right ventricular dysplasia 9	2021-07-26	criteria provided, single submitter	clinical testing	The p.Leu32Met variant in the PKP2gene has not been previously reported in association with disease. This variant was absent from large population databases, including the Genome Aggregation Database (http://gnomad.broadinstitute.org/). The leucine at position 32 is evolutionarily conserved. Computationaltools do not predict that the p.Leu32Met variant impacts protein function; however, the accuracy of in silicoalgorithms is limited. These data were assessed using the ACMG/AMP variant interpretation guidelines. In summary, the significance of thep.Leu32Metvariant is uncertain. Additional information is needed to resolve the significance of this variant. [ACMG evidence codes used: PM2]