Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000459856 | SCV000544804 | pathogenic | Familial aplasia of the vermis; Meckel-Gruber syndrome | 2023-08-20 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 406251). This sequence change creates a premature translational stop signal (p.Leu932Argfs*22) in the RPGRIP1L gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RPGRIP1L are known to be pathogenic (PMID: 17558409). This variant is present in population databases (rs778824093, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with RPGRIP1L-related conditions. |
| Ambry Genetics | RCV002526400 | SCV003556350 | pathogenic | Inborn genetic diseases | 2021-06-16 | criteria provided, single submitter | clinical testing | The c.2794_2795delTT (p.L932Rfs*22) alteration, located in exon 18 (coding exon 17) of the RPGRIP1L gene, consists of a deletion of 2 nucleotides from position 2794 to 2795, causing a translational frameshift with a predicted alternate stop codon after 22 amino acids. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. This alteration has been previously identified in the compound heterozygous state with a second RPGRIP1L variant, confirmed in trans by parental testing, in a patient with ciliopathy (Pajusalu, 2018). Based on the available evidence, this alteration is classified as pathogenic. |