ClinVar Miner

Submissions for variant NM_001943.5(DSG2):c.1376A>G (p.Tyr459Cys) (rs576404380)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000171268 SCV000697882 likely benign not provided 2016-02-01 criteria provided, single submitter clinical testing Variant summary: DSG2 c.1376A>G variant affects a conserved nucleotide, resulting in amino acid change from Tyr to Cys. 4/4 in-silico tools predict a damaging outcome for this variant, however, functional studies have not been carried out to confirm these predictions. This variant is found in 139/111860 control chromosomes (5 homozygotes) at a frequency of 0.0012426. The variant is predominantly found in South Asians (132/15646; 0.0084367). These frequencies are 124-843 times the maximal expected frequency of a pathogenic DSG2 allele (0.00001), highly suggesting this variant is benign. Additionally, the variant has been reported in 1 HCM patient to co-occur with a pathogenic variant, TNNT2 R92W. Although one research center reports this variant as likely pathogenic, they provide no evidence to independently evaluate. Taken together, this is probably a normal variant given the high frequency in controls and at least one reported co-occurrence with a pathogenic TNNT2 allele, thus this DSG2 variant was classified as likely benign.
GeneDx RCV000606666 SCV000714891 benign not specified 2017-04-19 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.
Ambry Genetics RCV000617986 SCV000737979 benign Cardiovascular phenotype 2017-04-07 criteria provided, single submitter clinical testing Insufficient evidence
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne RCV000755675 SCV000883080 uncertain significance Arrhythmogenic right ventricular cardiomyopathy, type 10 2018-11-21 criteria provided, single submitter clinical testing
Color Health, Inc RCV000776131 SCV000911079 benign Cardiomyopathy 2018-10-05 criteria provided, single submitter clinical testing
Invitae RCV000755675 SCV001003479 benign Arrhythmogenic right ventricular cardiomyopathy, type 10 2020-10-06 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000755675 SCV001284603 likely benign Arrhythmogenic right ventricular cardiomyopathy, type 10 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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000776131 SCV001334033 benign Cardiomyopathy 2018-03-12 criteria provided, single submitter clinical testing
Developmental Genetics Unit,King Faisal Specialist Hospital & Research Centre RCV000171268 SCV000221465 likely pathogenic not provided no assertion criteria provided research

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