ClinVar Miner

Submissions for variant NM_001943.5(DSG2):c.2234C>T (p.Thr745Met) (rs727504783)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000156101 SCV000205814 likely benign not specified 2013-10-15 criteria provided, single submitter clinical testing Thr745Met in exon 14 of DSG2: This variant is not expected to have clinical sign ificance due to a lack of conservation across species, including mammals. Of not e, 10 other species including mammals have a methionine (Met) at this position. In addition, computational analyses (AlignGVGD, PolyPhen2, SIFT) do not suggest a high likelihood of impact to the protein.
Illumina Clinical Services Laboratory,Illumina RCV000361252 SCV000408243 uncertain significance Arrhythmogenic right ventricular cardiomyopathy, type 10 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.
GeneDx RCV000766739 SCV000570923 uncertain significance not provided 2016-07-14 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the DSG2 gene. The T745M variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. This variant was not observed in approximately 6,300 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The T745M variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at a position that is not conserved across species, and Methionine is the wildtype amino acid at this position in multiple species. In silico analysis predicts this variant likely does not alter the protein structure/function. Furthermore, this variant has been classified in ClinVar as a likely benign variant by another clinical laboratory (ClinVar SCV000205814.3; Landrum et al., 2016). Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or benign.
Color Health, Inc RCV000777763 SCV000913729 likely benign Cardiomyopathy 2018-10-29 criteria provided, single submitter clinical testing
Invitae RCV000766739 SCV001014979 likely benign not provided 2018-08-26 criteria provided, single submitter clinical testing
Invitae RCV000361252 SCV001709345 likely benign Arrhythmogenic right ventricular cardiomyopathy, type 10 2020-08-14 criteria provided, single submitter clinical testing

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