Submissions for variant NM_001005242.3(PKP2):c.195C>T (p.Ala65=)

gnomAD frequency: 0.00015  dbSNP: rs397517014

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000038192	SCV000061859	likely benign	not specified	2015-05-27	criteria provided, single submitter	clinical testing	p.Ala65Ala in exon 1 of PKP2: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. It has been identified in 14/52344 European ch romosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute. org; dbSNP rs397517014).
GeneDx	RCV000038192	SCV000171019	benign	not specified	2014-03-22	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000560794	SCV000638876	likely benign	Arrhythmogenic right ventricular dysplasia 9	2024-01-04	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000617958	SCV000737630	likely benign	Cardiovascular phenotype	2016-07-13	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000560794	SCV000743463	likely benign	Arrhythmogenic right ventricular dysplasia 9	2017-07-28	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000776295	SCV000911589	likely benign	Cardiomyopathy	2018-10-02	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000560794	SCV001266943	uncertain significance	Arrhythmogenic right ventricular dysplasia 9	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000560794	SCV002048588	likely benign	Arrhythmogenic right ventricular dysplasia 9	2021-04-23	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV003996375	SCV004844470	likely benign	Arrhythmogenic right ventricular cardiomyopathy	2023-12-01	criteria provided, single submitter	clinical testing
Clinical Genetics, Academic Medical Center	RCV000038192	SCV001924273	benign	not specified		no assertion criteria provided	clinical testing