ClinVar Miner

Submissions for variant NM_001943.5(DSG2):c.806T>C (p.Ile269Thr) (rs727502986)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000150536 SCV000197750 uncertain significance not specified 2015-01-29 criteria provided, single submitter clinical testing The p.Ile269Thr variant in DSG2 has been reported in 1 individual with ARVC (Fre ssart 2010) and has been identified in 6/11544 of Latino chromosomes by the Exom e Aggregation Consortium (ExAC, http://exac.broadinstitute.org). Computational p rediction tools and conservation analysis do not provide strong support for or a gainst an impact to the protein. In summary, the clinical significance of the p. Ile269Thr variant is uncertain.
Invitae RCV001045466 SCV001209319 uncertain significance Arrhythmogenic right ventricular cardiomyopathy, type 10 2020-10-21 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with threonine at codon 269 of the DSG2 protein (p.Ile269Thr). The isoleucine residue is highly conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant is present in population databases (rs727502986, ExAC 0.05%). This variant has been observed in an individual affected with arrhythmogenic right ventricular cardiomyopathy (PMID: 20400443). ClinVar contains an entry for this variant (Variation ID: 163204). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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 RCV001181124 SCV001346210 uncertain significance Cardiomyopathy 2019-06-10 criteria provided, single submitter clinical testing
GeneDx RCV001563010 SCV001785876 uncertain significance not provided 2021-02-02 criteria provided, single submitter clinical testing Identified in a patient with arrhythmogenic right ventricular cardiomyopathy (ARVC) (Fressart et al., 2010); Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 163204; Landrum et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 20400443)

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