ClinVar Miner

Submissions for variant NM_024334.2(TMEM43):c.428C>T (p.Thr143Met) (rs544554435)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000247251 SCV000320075 uncertain significance Cardiovascular phenotype 2017-11-16 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Invitae RCV000642410 SCV000764087 uncertain significance Arrhythmogenic right ventricular cardiomyopathy, type 5 2018-05-04 criteria provided, single submitter clinical testing This sequence change replaces threonine with methionine at codon 143 of the TMEM43 protein (p.Thr143Met). The threonine residue is moderately conserved and there is a moderate physicochemical difference between threonine and methionine. This variant is present in population databases (rs544554435, ExAC 0.01%). This variant has not been reported in the literature in individuals with TMEM43-related disease. ClinVar contains an entry for this variant (Variation ID: 179489). 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: "Probably 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.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000156279 SCV000205997 uncertain significance not specified 2014-09-30 criteria provided, single submitter clinical testing The Thr143Met variant in TMEM43 has been previously identified by our laboratory in 1 individual with HCM. This variant was not identified in large population s tudies; however, it has been identified in 1/854 healthy control chromosomes (Ka pplinger 2011). Computational prediction tools and conservation analysis do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the Thr143Met variant is uncertain.

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