ClinVar Miner

Submissions for variant NM_024334.2(TMEM43):c.214G>A (p.Val72Met) (rs368603914)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000770180 SCV000901607 uncertain significance Cardiomyopathy 2017-01-09 criteria provided, single submitter clinical testing
GeneDx RCV000183947 SCV000236439 uncertain significance not provided 2018-09-10 criteria provided, single submitter clinical testing p.Val72Met (GTG>ATG): c.214 G>A in exon 3 in the TMEM43 gene (NM_024334.2).The V72M variant in the TMEM43 gene has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The V72M variant was not observed in approximately 6,500 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 V72M variant is a conservative amino acid substitution, which occurs at a position that is conserved in mammals. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret V72M as a variant of unknown significance. The variant is found in ARVC panel(s).
Invitae RCV000529049 SCV000642089 uncertain significance Arrhythmogenic right ventricular cardiomyopathy, type 5 2017-04-27 criteria provided, single submitter clinical testing This sequence change replaces valine with methionine at codon 72 of the TMEM43 protein (p.Val72Met). The valine residue is moderately conserved and there is a small physicochemical difference between valine and methionine. This variant is present in population databases (rs368603914, ExAC 0.002%) but has not been reported in the literature in individuals with a TMEM43-related disease. ClinVar contains an entry for this variant (Variation ID: 202124). 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: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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