Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001038512 | SCV001201982 | pathogenic | Leber congenital amaurosis 13 | 2024-01-31 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 233 of the RDH12 protein (p.Val233Glu). This variant is present in population databases (no rsID available, gnomAD 0.001%). This missense change has been observed in individual(s) with autosomal recessive early-onset retinal dystrophy and/or autosomal recessive retinitis pigmentosa (PMID: 32865313; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 837228). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. This variant disrupts the p.Val233 amino acid residue in RDH12. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 25910913, 29178642, 30372751). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001732019 | SCV001983705 | uncertain significance | not specified | 2021-09-13 | criteria provided, single submitter | clinical testing | Variant summary: RDH12 c.698_699delinsAA (p.Val233Glu) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 248938 control chromosomes (gnomAD). c.698_699delinsAA has been reported in the literature in a homozygous individual affected with early-onset retinal dystrophy (Sallum_2020). 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. A ClinVar submitter (evaluation after 2014) cites the variant as uncertain significance. Other variants affecting the same amino acid residue (e.g. p.Val233Leu, p.Val233Asp) have been classified by our laboratory and others (cited in ClinVar and HGMD), as pathogenic and disease-associated. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. |
| Baylor Genetics | RCV001038512 | SCV004208598 | likely pathogenic | Leber congenital amaurosis 13 | 2023-06-20 | criteria provided, single submitter | clinical testing |