ClinVar Miner

Submissions for variant NM_000252.2(MTM1):c.1420C>T (p.Arg474Ter) (rs587783792)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory,University of Chicago RCV000146414 SCV000193700 pathogenic Severe X-linked myotubular myopathy 2013-02-08 criteria provided, single submitter clinical testing
GeneDx RCV000523062 SCV000617413 pathogenic not provided 2018-08-06 criteria provided, single submitter clinical testing The R474X nonsense variant in the MTM1 gene has been reported previously in association with myotubular myopathy (Laporte et al., 1997; Herman et al., 2002; Biancalana et al., 2003). This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Furthermore, the R474X variant is not observed in large population cohorts (Lek et al., 2016). Therefore, we interpret R474X to be a pathogenic variant.
Invitae RCV000146414 SCV000634488 pathogenic Severe X-linked myotubular myopathy 2016-10-12 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal at codon 474 (p.Arg474*) of the MTM1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MTM1 are known to be pathogenic. This particular variant has been reported in the literature in multiple individuals affected with myotubular myopathy (PMID: 11793470, 18358876, 25957634, 9305655). ClinVar contains an entry for this variant (Variation ID: 158935). For these reasons, this variant has been classified as Pathogenic.

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