ClinVar Miner

Submissions for variant NM_000252.3(MTM1):c.614C>T (p.Pro205Leu)

dbSNP: rs587783841
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000146466 SCV000193754 pathogenic Severe X-linked myotubular myopathy 2013-02-08 criteria provided, single submitter clinical testing
Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego RCV000146466 SCV001445916 pathogenic Severe X-linked myotubular myopathy 2019-05-19 criteria provided, single submitter clinical testing This variant has been previously reported as a hemizygous change in males and as a heterozygous change in affected female carriers with X-linked myotubular myopathy (PMID: 8640223, 11793470, 28685322, 30047259). It is absent from the ExAC and gnomAD population databases and thus is presumed to be rare. The c.614C>T (p.Pro205Leu) variant is predicted by multiple in silico tools to have a deleterious effect on protein function. Based on the available evidence, the c.614C>T (p.Pro205Leu) variant is classified as Pathogenic.
GeneDx RCV001564887 SCV001788127 pathogenic not provided 2021-06-28 criteria provided, single submitter clinical testing Published functional studies suggest that P205L disrupts phosphatase activity (Taylor et al., 2000); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 11793470, 27535533, 10900271, 15725586, 10063835, 30047259, 28685322, 8640223)
Invitae RCV000146466 SCV002242511 pathogenic Severe X-linked myotubular myopathy 2022-12-08 criteria provided, single submitter clinical testing Experimental studies have shown that this missense change affects MTM1 function (PMID: 10900271). 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 expected to disrupt MTM1 protein function. ClinVar contains an entry for this variant (Variation ID: 158987). This variant is also known as C668T (P223L). This missense change has been observed in individual(s) with myotubular myopathy (PMID: 8640223, 11793470, 28685322). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 205 of the MTM1 protein (p.Pro205Leu). For these reasons, this variant has been classified as Pathogenic.
Revvity Omics, Revvity RCV001564887 SCV004238294 likely pathogenic not provided 2020-03-01 criteria provided, single submitter clinical testing

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