Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000634078 | SCV000755356 | likely pathogenic | Walker-Warburg congenital muscular dystrophy | 2022-06-27 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 307 of the FKTN protein (p.Arg307Gly). 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. This variant disrupts the p.Arg307 amino acid residue in FKTN. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 17044012, 19179078, 19396839, 25821721, 26923585, 30060766). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a 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 FKTN protein function. ClinVar contains an entry for this variant (Variation ID: 528827). This variant has not been reported in the literature in individuals affected with FKTN-related conditions. This variant is not present in population databases (gnomAD no frequency). |
| Natera, |
RCV000634078 | SCV002079607 | uncertain significance | Walker-Warburg congenital muscular dystrophy | 2020-07-25 | no assertion criteria provided | clinical testing |