Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002912888 | SCV003247991 | uncertain significance | Familial aplasia of the vermis; Meckel-Gruber syndrome | 2024-10-08 | 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 1277 of the RPGRIP1L protein (p.Ile1277Val). This variant is present in population databases (rs770410795, gnomAD 0.009%). 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: 2041138). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt RPGRIP1L protein function with a negative predictive value of 80%. 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. |
| Ambry Genetics | RCV002890970 | SCV003704327 | uncertain significance | Inborn genetic diseases | 2021-08-16 | criteria provided, single submitter | clinical testing | The c.3829A>G (p.I1277V) alteration is located in exon 26 (coding exon 25) of the RPGRIP1L gene. This alteration results from a A to G substitution at nucleotide position 3829, causing the isoleucine (I) at amino acid position 1277 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Fulgent Genetics, |
RCV005010760 | SCV005639864 | uncertain significance | Joubert syndrome 7; Meckel syndrome, type 5; COACH syndrome 3 | 2024-03-05 | criteria provided, single submitter | clinical testing | |
| Prevention |
RCV004545417 | SCV004766760 | uncertain significance | RPGRIP1L-related disorder | 2024-07-07 | no assertion criteria provided | clinical testing | The RPGRIP1L c.3829A>G variant is predicted to result in the amino acid substitution p.Ile1277Val. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0085% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |