Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001052013 | SCV001216201 | uncertain significance | Cone-rod dystrophy 6; Leber congenital amaurosis 1 | 2022-03-10 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 946 of the GUCY2D protein (p.Ala946Glu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with autosomal recessive inherited retinal disease (PMID: 28341476). ClinVar contains an entry for this variant (Variation ID: 848290). 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. This variant disrupts the p.Ala946 amino acid residue in GUCY2D. Other variant(s) that disrupt this residue have been observed in individuals with GUCY2D-related conditions (PMID: 16505055), which suggests that this may be a clinically significant amino acid residue. 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. |
| Genomics England Pilot Project, |
RCV001542698 | SCV001760420 | likely pathogenic | Cone-rod dystrophy 6 | no assertion criteria provided | clinical testing |