Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000521905 | SCV000618499 | uncertain significance | not provided | 2017-06-16 | criteria provided, single submitter | clinical testing | The Y659C variant in the RPGRIP1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The Y659C variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The Y659C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret Y659C as a variant of uncertain significance. |
Invitae | RCV001319192 | SCV001509925 | uncertain significance | Cone-rod dystrophy 13; Leber congenital amaurosis 6 | 2020-09-09 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine with cysteine at codon 659 of the RPGRIP1 protein (p.Tyr659Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with RPGRIP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 449984). 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. 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. |
Genome- |
RCV001800728 | SCV002044989 | uncertain significance | Leber congenital amaurosis 6 | 2021-11-07 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV001800729 | SCV002045000 | uncertain significance | Cone-rod dystrophy 13 | 2021-11-07 | criteria provided, single submitter | clinical testing |