Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000807104 | SCV000947140 | uncertain significance | Familial aplasia of the vermis; Meckel-Gruber syndrome | 2021-08-20 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with cysteine at codon 561 of the RPGRIP1L protein (p.Arg561Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs781713688, ExAC 0.02%). 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: 651693). 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. 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, |
RCV002487731 | SCV002783840 | uncertain significance | Joubert syndrome 7; Meckel syndrome, type 5; COACH syndrome 3 | 2022-02-15 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV001835971 | SCV002085720 | uncertain significance | Familial aplasia of the vermis | 2020-02-12 | no assertion criteria provided | clinical testing | |
Prevention |
RCV004733050 | SCV005362963 | uncertain significance | RPGRIP1L-related disorder | 2024-09-10 | no assertion criteria provided | clinical testing | The RPGRIP1L c.1681C>T variant is predicted to result in the amino acid substitution p.Arg561Cys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.023% of alleles in individuals of South 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. |