ClinVar Miner

Submissions for variant NM_001943.5(DSG2):c.1837G>A (p.Ala613Thr) (rs368257724)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000171904 SCV000050905 uncertain significance not provided 2013-06-24 criteria provided, single submitter research
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000037273 SCV000060930 uncertain significance not specified 2012-10-19 criteria provided, single submitter clinical testing The Ala613Thr variant in DSG2 has been previously reported in one infant with DC M tested by our laboratory. This variant has been identified in 1/847 control ch romosomes (Kapplinger 2011) and in 1/4202 African American chromosomes from a br oad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.e du/EVS/). Computational analyses (biochemical amino acid properties, conservatio n, AlignGVGD, PolyPhen2, and SIFT) do not provide strong support for or against an impact to the protein. Additional information is needed to fully assess the c linical significance of this variant.
Invitae RCV000642324 SCV000763993 uncertain significance Arrhythmogenic right ventricular cardiomyopathy, type 10 2018-01-11 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 613 of the DSG2 protein (p.Ala613Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs368257724, ExAC 0.02%). This variant has not been reported in the literature in individuals with DSG2-related disease. ClinVar contains an entry for this variant (Variation ID: 44288). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Color Health, Inc RCV001179085 SCV001343675 uncertain significance Cardiomyopathy 2019-03-12 criteria provided, single submitter clinical testing

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