ClinVar Miner

Submissions for variant NM_000252.2(MTM1):c.1261-10A>G (rs397518445)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory,University of Chicago RCV000011807 SCV000193676 pathogenic Severe X-linked myotubular myopathy 2013-02-08 criteria provided, single submitter clinical testing
GeneDx RCV000255138 SCV000322252 pathogenic not provided 2017-08-22 criteria provided, single submitter clinical testing The c.1261-10 A>G variant has been reported in multiple male individuals with myotubular myopathy who also had supportive histological findings on muscle biopsy (as IVS12-10 A>G using alternate nomenclature in de Gouyon et al., 1997; Bijarnia et al., 2010; MTM1 LOVD). The c.1261-10 A>G variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Studies have shown this variant may create a new acceptor splice site by adding three additional amino acids to the protein (de Gouyon et al., 1997). We interpret c.1261-10 A>G as a pathogenic variant.
Institute of Human Genetics,Klinikum rechts der Isar RCV000011807 SCV000680295 pathogenic Severe X-linked myotubular myopathy 2017-12-13 criteria provided, single submitter clinical testing
Invitae RCV000011807 SCV001225216 pathogenic Severe X-linked myotubular myopathy 2019-06-17 criteria provided, single submitter clinical testing This sequence change falls in intron 11 of the MTM1 gene. It does not directly change the encoded amino acid sequence of the MTM1 protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals affected with myotubular myopathy and was observed to segregate with disease in one family (PMID: 9285787, 20358311, 10502779, 15725586, 9450905). This variant is also known as IVS12-10A>G and A(1315-10)G in the literature. ClinVar contains an entry for this variant (Variation ID: 11058). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000011807 SCV000032040 pathogenic Severe X-linked myotubular myopathy 2000-01-01 no assertion criteria provided literature only
Clinical Molecular Genetics Laboratory,Johns Hopkins All Children's Hospital RCV000011807 SCV000920409 pathogenic Severe X-linked myotubular myopathy 2010-01-29 no assertion criteria provided clinical testing

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