ClinVar Miner

Submissions for variant NM_000252.2(MTM1):c.757C>T (p.Arg253Ter) (rs587783854)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory,University of Chicago RCV000146481 SCV000193771 pathogenic Severe X-linked myotubular myopathy 2013-02-08 criteria provided, single submitter clinical testing
GeneDx RCV000578589 SCV000680687 pathogenic not provided 2018-09-17 criteria provided, single submitter clinical testing The R253X variant in the MTM1 gene has been reported previously multiple times as a hemizygous variant in males with features consistent with severe myotubular myopathy (Flex et al., 2002; Biancalana et al., 2003; Longo et al., 2016; Savarese et al., 2016). The R253X variant was also reported in heterozygous state in a study looking at manifesting carriers in a single family with three females with mild muscle disease as well as multiple asymptomatic female relatives; however, X-inactivation studies did not demonstrate skewed X-inactivation in the symptomatic female carriers in this family (Grogan et al., 2005). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R253X variant is not observed in large population cohorts (Lek et al., 2016). We interpret R253X as a pathogenic variant.
Invitae RCV000146481 SCV001407235 pathogenic Severe X-linked myotubular myopathy 2019-10-16 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg253*) in the MTM1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with congenital myopathy (PMID: 9858861, 27017278, 12031625, 12522554, 15883335). ClinVar contains an entry for this variant (Variation ID: 159001). This variant is also known as p.R271X in the literature. Loss-of-function variants in MTM1 are known to be pathogenic (PMID: 9305655, 10063835). For these reasons, this variant has been classified as Pathogenic.
Clinical Molecular Genetics Laboratory,Johns Hopkins All Children's Hospital RCV000146481 SCV000920408 pathogenic Severe X-linked myotubular myopathy 2010-01-20 no assertion criteria provided clinical testing

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