Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001213020 | SCV001384633 | pathogenic | Familial aplasia of the vermis; Meckel-Gruber syndrome | 2022-06-02 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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 tolerated. ClinVar contains an entry for this variant (Variation ID: 942932). This missense change has been observed in individuals with Joubert syndrome (PMID: 22693042, 29620724). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs772900011, gnomAD 0.006%). This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 550 of the RPGRIP1L protein (p.Gln550Arg). |