Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
SIB Swiss Institute of Bioinformatics | RCV000754843 | SCV000930062 | likely pathogenic | Myopathy, centronuclear, 2 | 2019-01-08 | criteria provided, single submitter | curation | This variant is interpreted as a Likely pathogenic for Myopathy, centronuclear, 2 autosomal recessive. The following ACMG Tag(s) were applied: PM2 : Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PP3 : Multiple lines of computational evidence support a deleterious effect on the gene or gene product. PM1 : Located in a mutational hot spot and/or critical and well-established functional domain (e.g., active site of an enzyme) without benign variation. PP1-Strong : PP1 (segregation data) upgraded in strength to Strong (PMID:29950440). |
Invitae | RCV000754843 | SCV003786394 | pathogenic | Myopathy, centronuclear, 2 | 2021-12-15 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 617681). This missense change has been observed in individuals with autosomal recessive centronuclear myopathy (PMID: 29950440). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs777176261, gnomAD 0.003%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 234 of the BIN1 protein (p.Arg234Cys). |
OMIM | RCV000754843 | SCV000882723 | pathogenic | Myopathy, centronuclear, 2 | 2019-02-08 | no assertion criteria provided | literature only |