Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001059685 | SCV001224316 | uncertain significance | Cone-rod dystrophy 6; Leber congenital amaurosis 1 | 2021-09-17 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with tryptophan at codon 761 of the GUCY2D protein (p.Arg761Trp). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs200637525, ExAC 0.006%). This variant has been observed in individual(s) with autosomal recessive inherited retinal dystrophy (PMID: 29559409). This variant has been reported in individual(s) with autosomal dominant inherited retinal dystrophy (PMID: 32821499); however, the role of the variant in this condition is currently unclear. ClinVar contains an entry for this variant (Variation ID: 854601). 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. Experimental studies have shown that this variant affects GUCY2D protein function (PMID: 33109612). 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. |
| OMIM | RCV002290577 | SCV000992260 | pathogenic | Night blindness, congenital stationary, type1i | 2019-09-03 | no assertion criteria provided | literature only |