Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001379169 | SCV001576919 | likely pathogenic | not provided | 2023-09-21 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CNGB3 protein function. ClinVar contains an entry for this variant (Variation ID: 427673). This missense change has been observed in individual(s) with achromatopsia (PMID: 28795510). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 269 of the CNGB3 protein (p.Leu269Pro). |
| 3billion | RCV000497819 | SCV002058385 | likely pathogenic | Achromatopsia 3 | 2022-01-03 | criteria provided, single submitter | clinical testing | Same nucleotide change resulting in same amino acid change has been previously reported to be associated with CNGB3 related disorder (ClinVar ID: VCV000427673, PMID:28795510). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.751, 3CNET: 0.879, PP3_P). It is not observed in the gnomAD v2.1.1 dataset (PM2_M). The variant has been reported to be in trans with a pathogenic variant as either compound heterozygous or homozygous in at least one similarly affected unrelated individual (PMID: 28795510, PM3_M). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline. |
| Molecular Genetics Laboratory, |
RCV000497819 | SCV000575807 | likely pathogenic | Achromatopsia 3 | 2017-03-27 | no assertion criteria provided | research |