ClinVar Miner

Submissions for variant NM_024334.3(TMEM43):c.413A>G (p.Gln138Arg) (rs397517384)

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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 RCV000039385 SCV000063069 uncertain significance not specified 2014-09-25 criteria provided, single submitter clinical testing The Gln138Arg variant in TMEM43 has been identified by our laboratory in 2 indiv iduals with cardiomyopathy (1 with DCM and 1 with HCM who carried a pathogenic v ariant in another gene) and segregated with disease in 1 affected relative with DCM. Computational prediction tools and conservation analysis suggest that this variant may not impact the protein, though this information is not predictive en ough to rule out pathogenicity. In summary, the clinical significance of the Gln 138Arg variant is uncertain.
Invitae RCV001065074 SCV001230013 uncertain significance Arrhythmogenic right ventricular cardiomyopathy, type 5 2019-04-15 criteria provided, single submitter clinical testing This sequence change replaces glutamine with arginine at codon 138 of the TMEM43 protein (p.Gln138Arg). The glutamine residue is weakly conserved and there is a small physicochemical difference between glutamine and arginine. This variant is present in population databases (rs397517384, ExAC 0.01%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has not been reported in the literature in individuals with TMEM43-related conditions. ClinVar contains an entry for this variant (Variation ID: 46146). 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 tolerated, 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.
CeGaT Praxis fuer Humangenetik Tuebingen RCV001090467 SCV001246031 uncertain significance not provided 2019-10-01 criteria provided, single submitter clinical testing
Color RCV001178116 SCV001342472 uncertain significance Cardiomyopathy 2020-03-23 criteria provided, single submitter clinical testing

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