Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV001774186 | SCV001994716 | uncertain significance | not provided | 2020-02-03 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 29068140, 28838317) |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002282574 | SCV002572349 | likely pathogenic | Retinitis pigmentosa | 2022-08-03 | criteria provided, single submitter | clinical testing | Variant summary: CERKL c.316C>T (p.Arg106Cys) 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 5.2e-05 in 249812 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in CERKL causing Retinitis Pigmentosa (5.2e-05 vs 0.0013), allowing no conclusion about variant significance. c.316C>T has been reported in the literature as a homozygous and compound heterozygous genotype in at-least three individuals with features of inherited retinal disease undergoing genetic evaluations on large diagnostic panels (example, Wang_2017, Avela_2018, Sheck_2021 with secondary citations in Yohe_2020, Ellingford_2016, Downes_2020). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as uncertain significance citing overlapping but not identical evidence utilized in the context of this evaluation. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Fulgent Genetics, |
RCV002488562 | SCV002776556 | likely pathogenic | Retinitis pigmentosa 26 | 2024-06-10 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001774186 | SCV003524714 | pathogenic | not provided | 2025-01-13 | 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 106 of the CERKL protein (p.Arg106Cys). This variant is present in population databases (rs569826109, gnomAD 0.02%). This missense change has been observed in individuals with retinal dystrophy (PMID: 28838317, 29068140, 31816670, 35119454). ClinVar contains an entry for this variant (Variation ID: 1308275). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt CERKL protein function with a positive predictive value of 95%. This variant disrupts the p.Arg106 amino acid residue in CERKL. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 18978954). 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. |
| Baylor Genetics | RCV002488562 | SCV004216782 | pathogenic | Retinitis pigmentosa 26 | 2024-03-28 | criteria provided, single submitter | clinical testing |