Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001327126 | SCV001518188 | likely pathogenic | Walker-Warburg congenital muscular dystrophy | 2023-08-20 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 316 of the FKRP protein (p.Pro316Ala). This variant has not been reported in the literature in individuals affected with FKRP-related conditions. ClinVar contains an entry for this variant (Variation ID: 1026650). 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 FKRP protein function. This variant disrupts the p.Pro316 amino acid residue in FKRP. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11592034, 11741828, 16368217, 25135358). 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. |
| Natera, |
RCV001831029 | SCV002091325 | uncertain significance | Autosomal recessive limb-girdle muscular dystrophy type 2I | 2021-04-02 | no assertion criteria provided | clinical testing |