ClinVar Miner

Submissions for variant NM_024334.3(TMEM43):c.280G>A (p.Ala94Thr)

gnomAD frequency: 0.00014  dbSNP: rs369142200
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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, Mass General Brigham Personalized Medicine RCV000154853 SCV000204535 uncertain significance not specified 2015-05-16 criteria provided, single submitter clinical testing The p.Ala94Thr variant in TMEM43 has not been reported in any other families wit h DCM, but has been identified in 7/10236 African chromosomes by the Exome Aggre gation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs369142200). Com putational prediction tools and conservation analysis do not provide strong supp ort for or against an impact to the protein. In summary, the clinical significan ce of the p.Ala94Thr variant is uncertain.
Ambry Genetics RCV000618582 SCV000736637 benign Cardiovascular phenotype 2022-09-30 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Labcorp Genetics (formerly Invitae), Labcorp RCV000642414 SCV000764092 uncertain significance Arrhythmogenic right ventricular dysplasia 5 2023-11-05 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 94 of the TMEM43 protein (p.Ala94Thr). This variant is present in population databases (rs369142200, gnomAD 0.06%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with TMEM43-related conditions. ClinVar contains an entry for this variant (Variation ID: 178138). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt TMEM43 protein function with a negative predictive value of 80%. 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 Diagnostics, LLC DBA Color Health RCV001189966 SCV001357367 likely benign Cardiomyopathy 2021-01-07 criteria provided, single submitter clinical testing

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