Submissions for variant NM_024422.6(DSC2):c.370C>T (p.His124Tyr)

dbSNP: rs371443698

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000181176	SCV000233453	benign	not specified	2015-05-19	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.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000181176	SCV000269039	benign	not specified	2015-04-01	criteria provided, single submitter	clinical testing	p.His124Tyr in exon 4 of DSC2: This variant is not expected to have clinical sig nificance because it has been identified in 1.4% (236/16370) of South Asian chro mosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.or g; dbSNP rs371443698).
Invitae	RCV001080415	SCV000645015	benign	Arrhythmogenic right ventricular dysplasia 11	2024-01-30	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000587969	SCV000699500	benign	not provided	2017-03-27	criteria provided, single submitter	clinical testing	Variant summary: The DSC2 c.370C>T (p.His124Tyr) variant involves the alteration of a non-conserved nucleotide. 4/4 in silico tools predict a benign outcome for this variant (SNPs&GO not captured due to low reliability index). This variant was found in 240/119242 control chromosomes (1 homozygote), predominantly observed in the South Asian subpopulation at a frequency of 0.014417 (236/16370). This frequency is about 1442 times the estimated maximal expected allele frequency of a pathogenic DSC2 variant (0.00001), suggesting this is likely a benign polymorphism found primarily in the populations of South Asian origin. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign. Taken together, this variant is classified as benign.
Ambry Genetics	RCV000617594	SCV000738262	benign	Cardiovascular phenotype	2017-12-26	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.
Color Diagnostics, LLC DBA Color Health	RCV000776122	SCV000911004	benign	Cardiomyopathy	2018-03-09	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001080415	SCV001282914	uncertain significance	Arrhythmogenic right ventricular dysplasia 11	2017-04-27	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.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000776122	SCV001334029	benign	Cardiomyopathy	2018-01-12	criteria provided, single submitter	clinical testing