Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002568950 | SCV003305339 | pathogenic | Qualitative or quantitative defects of dysferlin | 2022-04-26 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1867 of the DYSF protein (p.Phe1867Leu). This variant is present in population databases (no rsID available, gnomAD 0.007%). This missense change has been observed in individual(s) with Myoshi myopathy (PMID: 21392994). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 1184483). 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 DYSF protein function. For these reasons, this variant has been classified as Pathogenic. |
Genomics England Pilot Project, |
RCV001542524 | SCV001760095 | likely pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2B | no assertion criteria provided | clinical testing |