ClinVar Miner

Submissions for variant NM_000252.2(MTM1):c.575A>G (p.Tyr192Cys) (rs587783838)

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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 RCV000146463 SCV000193751 likely pathogenic Severe X-linked myotubular myopathy 2015-04-10 criteria provided, single submitter clinical testing
Invitae RCV000146463 SCV000634492 likely pathogenic Severe X-linked myotubular myopathy 2019-06-21 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with cysteine at codon 192 of the MTM1 protein (p.Tyr192Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is not present in population databases (rs587783838, ExAC no frequency). This variant has been reported in several individuals affected with myotubular myopathy (PMID: 20434914, Invitae). ClinVar contains an entry for this variant (Variation ID: 158984). Experimental studies have shown that this missense change results in lower MTM1 protein levels than the wild type (PMID: 20434914). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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