Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001879810 | SCV002238608 | pathogenic | Cone-rod dystrophy 6; Leber congenital amaurosis 1 | 2021-09-17 | criteria provided, single submitter | clinical testing | 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. For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Gly1013 amino acid residue in GUCY2D. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 28966547, 32165824). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 974654). This missense change has been observed in individual(s) with Leber congenital amaurosis (PMID: 26047050; Invitae). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with arginine at codon 1013 of the GUCY2D protein (p.Gly1013Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. |
| Laboratory of Genetics in Ophthalmology, |
RCV001250854 | SCV001426346 | likely pathogenic | Leber congenital amaurosis 1 | no assertion criteria provided | research |