ClinVar Miner

Submissions for variant NM_152263.4(TPM3):c.758C>A (p.Thr253Lys) (rs1553248515)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000524673 SCV000635070 pathogenic Nemaline myopathy 1; Congenital myopathy with fiber type disproportion 2017-08-16 criteria provided, single submitter clinical testing This sequence change replaces threonine with lysine at codon 253 of the TPM3 protein (p.Thr253Lys). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and lysine. This variant is not present in population databases (ExAC no frequency). This variant has been shown to arise de novo in an individual affected with congenital myopathy (PMID: 24692096). In addition, family studies have indicated that this variant was not present in the parents of an individual with congenital myopathy with dilated cardiomyopathy, which suggests that it was de novo in that affected individual (Invitae). 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 disruptive, but these predictions have not been confirmed by published functional studies. For these reasons, this variant has been classified as Pathogenic.

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