Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001986777 | SCV002286761 | uncertain significance | Walker-Warburg congenital muscular dystrophy | 2022-10-13 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 236 of the FKTN protein (p.Met236Arg). This variant is present in population databases (rs769033293, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with FKTN-related conditions. ClinVar contains an entry for this variant (Variation ID: 1493837). 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 not expected to disrupt FKTN protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Ambry Genetics | RCV004616947 | SCV005118158 | uncertain significance | Cardiovascular phenotype | 2024-04-13 | criteria provided, single submitter | clinical testing | The p.M236R variant (also known as c.707T>G), located in coding exon 5 of the FKTN gene, results from a T to G substitution at nucleotide position 707. The methionine at codon 236 is replaced by arginine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |