ClinVar Miner

Submissions for variant NM_000252.2(MTM1):c.342_342+4del (rs797045717)

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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 RCV000195024 SCV000248086 pathogenic Severe X-linked myotubular myopathy 2013-02-08 criteria provided, single submitter clinical testing
GeneDx RCV000256076 SCV000322251 pathogenic not provided 2015-12-17 criteria provided, single submitter clinical testing The c.342_342+4delAGTAA pathogenic variant in the MTM1 gene has been reported previously in a male individual with myotubular myopathy (Laporte et al., 2000). This deletion spans the splice junction and destroys the canonical splice donor site in intron 5. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. The c.342_342+4delAGTAA variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret c.342_342+4delAGTAA as a pathogenic variant.
Invitae RCV000195024 SCV000940029 pathogenic Severe X-linked myotubular myopathy 2018-11-20 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 5 of the MTM1 gene. It is expected to disrupt RNA splicing and likely results 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 X-linked myotubular myopathy (PMID: 9285787, 29567349). This variant is also known as delta392-396GTAAA in the literature. ClinVar contains an entry for this variant (Variation ID: 211532). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in MTM1 are known to be pathogenic (PMID: 9305655, 10063835). For these reasons, this variant has been classified as Pathogenic.
Athena Diagnostics Inc RCV000256076 SCV001144595 pathogenic not provided 2019-05-08 criteria provided, single submitter clinical testing The variant results in a shift of the reading frame, and is therefore predicted to result in the loss of a functional protein. Found in at least one symptomatic patient, and not found in general population data.
Clinical Molecular Genetics Laboratory,Johns Hopkins All Children's Hospital RCV000195024 SCV000920400 pathogenic Severe X-linked myotubular myopathy 2005-09-12 no assertion criteria provided clinical testing

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