Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| SIB Swiss Institute of Bioinformatics | RCV000754844 | SCV000930063 | 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 : Cosegregation with disease in multiple affected family members in a gene definitively known to cause the disease (PMID:29950440). PM3 : For recessive disorders, detected in trans with a pathogenic variant. |
| Invitae | RCV000754844 | SCV002252306 | likely pathogenic | Myopathy, centronuclear, 2 | 2023-03-10 | criteria provided, single submitter | clinical testing | This variant is present in population databases (no rsID available, gnomAD 0.0009%). 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt BIN1 protein function. ClinVar contains an entry for this variant (Variation ID: 617682). This missense change has been observed in individual(s) with autosomal recessive centronuclear myopathy (PMID: 29950440). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 145 of the BIN1 protein (p.Arg145Cys). |
| OMIM | RCV000754844 | SCV000882724 | pathogenic | Myopathy, centronuclear, 2 | 2019-02-08 | no assertion criteria provided | literature only |