Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Fulgent Genetics, |
RCV002504411 | SCV002815873 | uncertain significance | Joubert syndrome 7; Meckel syndrome, type 5; COACH syndrome 3 | 2024-05-06 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV002542955 | SCV002953799 | uncertain significance | Familial aplasia of the vermis; Meckel-Gruber syndrome | 2022-10-03 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 535 of the RPGRIP1L protein (p.Arg535His). This variant is present in population databases (rs371028848, gnomAD 0.07%). 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: 992033). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt RPGRIP1L 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. |
Prevention |
RCV004538557 | SCV004120511 | uncertain significance | RPGRIP1L-related disorder | 2022-11-23 | criteria provided, single submitter | clinical testing | The RPGRIP1L c.1604G>A variant is predicted to result in the amino acid substitution p.Arg535His. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.075% of alleles in individuals of South Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/16-53690479-C-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
Natera, |
RCV001280346 | SCV001467522 | uncertain significance | Familial aplasia of the vermis | 2020-04-24 | no assertion criteria provided | clinical testing |