Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genetic Services Laboratory, |
RCV000146411 | SCV000193697 | pathogenic | Severe X-linked myotubular myopathy | 2013-02-08 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000146411 | SCV000634487 | uncertain significance | Severe X-linked myotubular myopathy | 2017-04-29 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine with arginine at codon 469 of the MTM1 protein (p.His469Arg). The histidine residue is highly conserved and there is a small physicochemical difference between histidine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with X-linked myotubular myopathy (PMID: 17537630). ClinVar contains an entry for this variant (Variation ID: 158932). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). A different missense substitution at this codon (p.His469Pro) has been reported in an affected individual, but the clinical significance of this observation is unknown (PMID: 9305655). In summary, this variant is a rare missense change with uncertain impact on protein function. While it is absent from the population and reported in affected individuals, the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |