Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001940460 | SCV002192156 | uncertain significance | Cone-rod dystrophy 13; Leber congenital amaurosis 6 | 2022-01-20 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 318 of the RPGRIP1 protein (p.Ala318Val). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with clinical features of RPGRIP1-related conditions (PMID: 21224891). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003490944 | SCV004240985 | uncertain significance | not specified | 2023-12-12 | criteria provided, single submitter | clinical testing | Variant summary: RPGRIP1 c.953C>T (p.Ala318Val) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8.3e-06 in 242032 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.953C>T has been reported in the literature in one individual affected with primary open angle glaucoma, without strong evidence for causality (example, Fernandez-Martinez_2011). These report(s) do not provide unequivocal conclusions about association of the variant with Leber Congenital Amaurosis. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 21224891). One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |