Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001982516 | SCV002223396 | pathogenic | not provided | 2024-11-11 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 401 of the CNGA3 protein (p.Ser401Pro). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This missense change has been observed in individual(s) with achromatopsia and/or cone-rod dystrophy (PMID: 15712225, 30711023, 35119454). 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: 1444626). 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) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on CNGA3 protein function. For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV005057819 | SCV005725693 | pathogenic | Achromatopsia 2 | 2024-11-26 | criteria provided, single submitter | clinical testing | Variant summary: CNGA3 c.1201T>C (p.Ser401Pro) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 250344 control chromosomes. c.1201T>C has been reported in the literature in multiple individuals affected with cone-rod dystrophy and achromatopsia (e.g, Del Pozo-Valero_2022, Nishiguchi_2005, Sun_2019). These data indicate that the variant is very likely to be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 35119454, 15712225, 30711023). ClinVar contains an entry for this variant (Variation ID: 1444626). Based on the evidence outlined above, the variant was classified as pathogenic. |