Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000128837 | SCV001496650 | likely pathogenic | Polyglucosan body myopathy type 1 | 2023-04-13 | criteria provided, single submitter | clinical testing | This missense change has been observed in individual(s) with clinical features of RBCK1-related conditions (PMID: 23798481, 31127727). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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 RBCK1 protein function. ClinVar contains an entry for this variant (Variation ID: 140626). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 387 of the RBCK1 protein (p.Asn387Ser). |
| OMIM | RCV001840047 | SCV000172493 | pathogenic | Polyglucosan body myopathy 1 without immunodeficiency | 2013-12-01 | no assertion criteria provided | literature only |