ClinVar Miner

Submissions for variant NM_000252.2(MTM1):c.1204G>A (p.Gly402Arg) (rs1569565525)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000700810 SCV000829582 likely pathogenic Severe X-linked myotubular myopathy 2018-08-14 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 402 of the MTM1 protein (p.Gly402Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in several individuals affected with X-linked myotubular myopathy (XLMTM) (PMID:10063835, 11793470, 12031625). 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 and their clinical significance is uncertain. Other missense substitutions at this codon (p.Gly402Ala and p.Gly402Val) have been reported in individuals affected with XLMTM (PMID: 9305655, 9829274). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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