Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001316865 | SCV001507505 | uncertain significance | Cone-rod dystrophy 6; Leber congenital amaurosis 1 | 2021-07-20 | criteria provided, single submitter | clinical testing | 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.Pro858 amino acid residue in GUCY2D. Other variant(s) that disrupt this residue have been observed in individuals with GUCY2D-related conditions (PMID: 11035546), which suggests that this may be a clinically significant amino acid residue. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been observed in individual(s) with clinical features of cone-rod dystrophy (Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with threonine at codon 858 of the GUCY2D protein (p.Pro858Thr). The proline residue is highly conserved and there is a small physicochemical difference between proline and threonine. |