Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000668931 | SCV000793609 | uncertain significance | Autosomal recessive limb-girdle muscular dystrophy type 2A | 2017-08-30 | criteria provided, single submitter | clinical testing | |
Eurofins Ntd Llc |
RCV000728828 | SCV000856445 | uncertain significance | not provided | 2017-08-22 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000668931 | SCV002186876 | likely pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2A | 2023-12-02 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 401 of the CAPN3 protein (p.Tyr401Cys). This variant is present in population databases (rs371784007, gnomAD 0.01%). This missense change has been observed in individual(s) with clinical features of autosomal recessive limb-girdle muscular dystrophy (PMID: 15689361, 19556129, 27066573). ClinVar contains an entry for this variant (Variation ID: 553468). 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%. This variant disrupts the p.Tyr401 amino acid residue in CAPN3. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 33337384; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. |
Fulgent Genetics, |
RCV002507166 | SCV002815453 | uncertain significance | Autosomal recessive limb-girdle muscular dystrophy type 2A; Muscular dystrophy, limb-girdle, autosomal dominant 4 | 2021-11-09 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000728828 | SCV004012481 | likely pathogenic | not provided | 2023-06-14 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 27066573, 15689361, 19556129) |