Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001246611 | SCV001419981 | uncertain significance | Familial aplasia of the vermis; Meckel-Gruber syndrome | 2022-09-07 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 535 of the RPGRIP1L protein (p.Arg535Cys). This variant is present in population databases (rs149781516, gnomAD 0.03%). 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: 970944). 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. 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, |
RCV002484380 | SCV002791600 | uncertain significance | Joubert syndrome 7; Meckel syndrome, type 5; COACH syndrome 3 | 2024-04-30 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002570345 | SCV003607045 | uncertain significance | Inborn genetic diseases | 2022-03-29 | criteria provided, single submitter | clinical testing | The c.1603C>T (p.R535C) alteration is located in exon 14 (coding exon 13) of the RPGRIP1L gene. This alteration results from a C to T substitution at nucleotide position 1603, causing the arginine (R) at amino acid position 535 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Gene |
RCV004762020 | SCV005371284 | uncertain significance | not provided | 2023-06-13 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Natera, |
RCV001835274 | SCV002085727 | uncertain significance | Familial aplasia of the vermis | 2020-05-08 | no assertion criteria provided | clinical testing | |
Prevention |
RCV004538519 | SCV004113965 | uncertain significance | RPGRIP1L-related disorder | 2023-12-21 | no assertion criteria provided | clinical testing | The RPGRIP1L c.1603C>T variant is predicted to result in the amino acid substitution p.Arg535Cys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.036% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |