Submissions for variant NM_024422.6(DSC2):c.1559T>C (p.Ile520Thr)

gnomAD frequency: 0.00029  dbSNP: rs561310777

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000553381	SCV000644993	likely benign	Arrhythmogenic right ventricular dysplasia 11	2023-10-24	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000770537	SCV000901984	benign	Cardiomyopathy	2017-10-19	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000553381	SCV001288110	uncertain significance	Arrhythmogenic right ventricular dysplasia 11	2018-01-13	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.
Color Diagnostics, LLC DBA Color Health	RCV000770537	SCV001347319	likely benign	Cardiomyopathy	2018-11-16	criteria provided, single submitter	clinical testing
GeneDx	RCV001568859	SCV001792802	uncertain significance	not provided	2019-03-26	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; Reported in ClinVar but additional evidence is not available (ClinVar Variant ID# 155783; Landrum et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect
Ambry Genetics	RCV002399511	SCV002704940	likely benign	Cardiovascular phenotype	2019-12-26	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.
Blueprint Genetics	RCV000143880	SCV000188749	likely benign	Primary dilated cardiomyopathy	2014-06-18	no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001568859	SCV001978108	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001568859	SCV001979488	likely benign	not provided		no assertion criteria provided	clinical testing