Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genetics and Molecular Pathology, |
RCV001731225 | SCV001981639 | likely pathogenic | Macular corneal dystrophy | 2021-10-12 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001731225 | SCV003453847 | pathogenic | Macular corneal dystrophy | 2023-05-19 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Trp333 amino acid residue in CHST6. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 20539220). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 CHST6 protein function. ClinVar contains an entry for this variant (Variation ID: 1300206). This missense change has been observed in individuals with corneal macular dystrophy (PMID: 32472422, 35985662; Invitae). This variant is present in population databases (rs758657734, gnomAD 0.003%). This sequence change replaces tryptophan, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 333 of the CHST6 protein (p.Trp333Arg). |
MGZ Medical Genetics Center | RCV001731225 | SCV002581213 | uncertain significance | Macular corneal dystrophy | 2021-10-21 | flagged submission | clinical testing |