ClinVar Miner

Submissions for variant NM_000252.2(MTM1):c.1353G>A (p.Gln451=) (rs587783781)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory,University of Chicago RCV000146402 SCV000193688 uncertain significance Severe X-linked myotubular myopathy 2013-02-08 criteria provided, single submitter clinical testing
Invitae RCV000146402 SCV001391223 pathogenic Severe X-linked myotubular myopathy 2019-07-31 criteria provided, single submitter clinical testing This sequence change affects codon 451 of the MTM1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the MTM1 protein. This variant also falls at the last nucleotide of exon 12 of the MTM1 coding sequence, which is part of the consensus splice site for this exon. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with MTM1-related myopathy and was observed de novo in at least one individual (PMID: 10790201, Invitae). ClinVar contains an entry for this variant (Variation ID: 158923). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). 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.

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