Submissions for variant NM_001005242.3(PKP2):c.2260A>G (p.Thr754Ala)

gnomAD frequency: 0.00231  dbSNP: rs112592855

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000038208	SCV000054791	benign	not specified	2013-06-24	criteria provided, single submitter	research
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000038208	SCV000061876	likely benign	not specified	2017-05-18	criteria provided, single submitter	clinical testing	p.Thr798Ala in exon 12 of PKP2: This variant is not expected to have clinical si gnificance because it has been identified in 0.8% (181/24012) of African chromos omes, including 1 homozygote, by the Genome Aggregation Database (gnomAD, http:/ /gnomad.broadinstitute.org/; dbSNP rs112592855).
GeneDx	RCV000038208	SCV000236189	benign	not specified	2015-05-06	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.
Invitae	RCV000988811	SCV000288605	benign	Arrhythmogenic right ventricular dysplasia 9	2024-01-28	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000622171	SCV000735591	benign	Cardiovascular phenotype	2018-03-12	criteria provided, single submitter	clinical testing	This alteration is classified as 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.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000769387	SCV000900779	benign	Cardiomyopathy	2023-05-16	criteria provided, single submitter	clinical testing
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	RCV000845408	SCV000987474	benign	Primary familial hypertrophic cardiomyopathy		criteria provided, single submitter	clinical testing
Mendelics	RCV000988811	SCV001138677	benign	Arrhythmogenic right ventricular dysplasia 9	2019-05-28	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000988811	SCV001272956	uncertain significance	Arrhythmogenic right ventricular dysplasia 9	2018-02-06	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Color Diagnostics, LLC DBA Color Health	RCV000769387	SCV001353182	benign	Cardiomyopathy	2018-04-13	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000988811	SCV002506104	likely benign	Arrhythmogenic right ventricular dysplasia 9	2022-06-30	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003964857	SCV004779539	likely benign	PKP2-related disorder	2020-01-27	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Clinical Genetics, Academic Medical Center	RCV000038208	SCV001917360	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001727534	SCV001969432	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001727534	SCV001979396	likely benign	not provided		no assertion criteria provided	clinical testing