Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV003801846 | SCV004597105 | uncertain significance | Cone-rod dystrophy 6; Leber congenital amaurosis 1 | 2023-06-21 | criteria provided, single submitter | clinical testing | This missense change has been observed in individual(s) with leber congenital amaurosis (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 980 of the GUCY2D protein (p.His980Tyr). 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 GUCY2D 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. This variant disrupts the p.His980 amino acid residue in GUCY2D. Other variant(s) that disrupt this residue have been observed in individuals with GUCY2D-related conditions (PMID: 17964524), which suggests that this may be a clinically significant amino acid residue. |