Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genetic Services Laboratory, |
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 | 2021-10-03 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Experimental studies have shown that this missense change affects MTM1 function (PMID: 20434914). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 158984). This missense change has been observed in individuals with myotubular myopathy (PMID: 20434914; Invitae). This variant is not present in population databases (ExAC no frequency). 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. 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. |
Gene |
RCV003329244 | SCV004036299 | likely pathogenic | not provided | 2023-03-22 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: Magot2014[abstract], 29668875, 34011573, 20434914) |