Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001242577 | SCV001415673 | uncertain significance | Familial aplasia of the vermis; Meckel-Gruber syndrome | 2022-08-22 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with threonine, which is neutral and polar, at codon 627 of the RPGRIP1L protein (p.Lys627Thr). This variant is present in population databases (rs377035693, gnomAD 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: 967617). 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. |
Genome Diagnostics Laboratory, |
RCV002294449 | SCV002587160 | uncertain significance | Kidney disorder | 2016-12-12 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002564033 | SCV003756724 | uncertain significance | Inborn genetic diseases | 2021-10-06 | criteria provided, single submitter | clinical testing | The c.1880A>C (p.K627T) alteration is located in exon 15 (coding exon 14) of the RPGRIP1L gene. This alteration results from a A to C substitution at nucleotide position 1880, causing the lysine (K) at amino acid position 627 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Natera, |
RCV001280341 | SCV001467517 | uncertain significance | Familial aplasia of the vermis | 2020-04-24 | no assertion criteria provided | clinical testing | |
Prevention |
RCV004538506 | SCV004727049 | uncertain significance | RPGRIP1L-related disorder | 2024-06-04 | no assertion criteria provided | clinical testing | The RPGRIP1L c.1880A>C variant is predicted to result in the amino acid substitution p.Lys627Thr. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.016% 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. |