Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002044181 | SCV002112286 | uncertain significance | Familial aplasia of the vermis; Meckel-Gruber syndrome | 2022-08-22 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 34 of the RPGRIP1L protein (p.Arg34Gly). This variant is present in population databases (rs565245381, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with RPGRIP1L-related conditions. ClinVar contains an entry for this variant (Variation ID: 1348157). 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: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. |
Fulgent Genetics, |
RCV002482418 | SCV002791101 | uncertain significance | Joubert syndrome 7; Meckel syndrome, type 5; COACH syndrome 3 | 2022-03-10 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV004536364 | SCV004717321 | uncertain significance | RPGRIP1L-related disorder | 2024-01-29 | no assertion criteria provided | clinical testing | The RPGRIP1L c.100C>G variant is predicted to result in the amino acid substitution p.Arg34Gly. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.054% of alleles in individuals of East Asian descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |