ClinVar Miner

Submissions for variant NM_024334.3(TMEM43):c.13T>C (p.Tyr5His)

gnomAD frequency: 0.00001  dbSNP: rs727505249
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Total submissions: 3
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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 RCV000156770 SCV000206491 uncertain significance not specified 2014-08-21 criteria provided, single submitter clinical testing The Tyr5His variant in TMEM43 has not been previously reported in individuals wi th cardiomyopathy or in large population studies. Computational prediction tools and conservation analysis do not provide strong support for or against an impac t to the protein. This variant is located in the first base of the exon, which i s part of the 3? splice region. Computational tools do not suggest an impact to splicing. However, this information is not predictive enough to rule out pathoge nicity. In summary, the clinical significance of the Tyr5His variant is uncertai n.
Color Diagnostics, LLC DBA Color Health RCV001177858 SCV001342140 uncertain significance Cardiomyopathy 2023-04-21 criteria provided, single submitter clinical testing This missense variant replaces tyrosine with histidine at codon 5 of the TMEM43 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with TMEM43-related disorders in the literature. This variant has been identified in 1/250764 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Invitae RCV001345124 SCV001539225 uncertain significance Arrhythmogenic right ventricular dysplasia 5 2021-08-27 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with histidine at codon 5 of the TMEM43 protein (p.Tyr5His). The tyrosine residue is moderately conserved and there is a moderate physicochemical difference between tyrosine and histidine. This variant is present in population databases (rs727505249, ExAC 0.002%). 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: 179967). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or 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.

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