Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000391985 | SCV000340121 | uncertain significance | not provided | 2016-03-17 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000534527 | SCV000645501 | pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2A | 2023-12-19 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with lysine, which is basic and polar, at codon 123 of the CAPN3 protein (p.Gln123Lys). This variant is present in population databases (no rsID available, gnomAD 0.01%). This missense change has been observed in individual(s) with autosomal recessive CAPN3-related conditions (Invitae; external communication). 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. ClinVar contains an entry for this variant (Variation ID: 286615). 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 CAPN3 protein function with a positive predictive value of 80%. For these reasons, this variant has been classified as Pathogenic. |