Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001880700 | SCV002142555 | uncertain significance | Familial aplasia of the vermis; Meckel-Gruber syndrome | 2022-05-19 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 723 of the RPGRIP1L protein (p.Ile723Val). This variant is present in population databases (rs769280712, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with RPGRIP1L-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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, |
RCV002490073 | SCV002783886 | uncertain significance | Joubert syndrome 7; Meckel syndrome, type 5; COACH syndrome 3 | 2022-02-17 | criteria provided, single submitter | clinical testing | |
| Prevention |
RCV004538566 | SCV004752699 | uncertain significance | RPGRIP1L-related disorder | 2024-04-16 | no assertion criteria provided | clinical testing | The RPGRIP1L c.2167A>G variant is predicted to result in the amino acid substitution p.Ile723Val. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.029% of alleles in individuals of Latino descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |