Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001318325 | SCV001509023 | pathogenic | not provided | 2024-01-29 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Tyr251*) in the RLBP1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 67 amino acid(s) of the RLBP1 protein. This variant is present in population databases (rs151141842, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with RLBP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 829822). This variant disrupts a region of the RLBP1 protein in which other variant(s) (p.Gln278*) have been determined to be pathogenic (PMID: 33851411). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
| Gene |
RCV001318325 | SCV001813734 | likely pathogenic | not provided | 2019-11-21 | criteria provided, single submitter | clinical testing | Nonsense variant in the C-terminus predicted to result in protein truncation, as the last 67 amino acids are lost, and other loss-of-function variants have been reported downstream in the Human Gene Mutation Database (Stenson et al., 2014); Has not been previously published as pathogenic or benign to our knowledge |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001844262 | SCV002103451 | likely pathogenic | Retinitis pigmentosa | 2022-02-25 | criteria provided, single submitter | clinical testing | Variant summary: RLBP1 c.753C>A (p.Tyr251X) results in a premature termination codon that is not expected to cause nonsense mediated decay (NMD), but is predicted to cause a truncation of the encoded protein, removing a part of the CRAL-TRIO lipid binding domain (amino acids 136-297; IPR001251). Truncations downstream of this position have been reported in individuals affected with retinitis pigmentosa (HGMD). The variant allele was found at a frequency of 8.6e-06 in 233170 control chromosomes (gnomAD). c.753C>A has been reported in the literature in one homozygous individual affected with retinal dystrophy (Bocquet_2021). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three ClinVar submitters have assessed the variant since 2014: one classified the variant as of uncertain significance, and two as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Bioscientia Institut fuer Medizinische Diagnostik Gmb |
RCV001029758 | SCV001192536 | likely pathogenic | Pigmentary retinal dystrophy | 2019-04-02 | no assertion criteria provided | clinical testing |