Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002949231 | SCV003284438 | uncertain significance | Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis | 2024-10-22 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 468 of the CEP290 protein (p.Cys468Tyr). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with CEP290-related conditions. ClinVar contains an entry for this variant (Variation ID: 2071157). 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 not expected to disrupt CEP290 protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Prevention |
RCV004536491 | SCV004750247 | uncertain significance | CEP290-related disorder | 2024-01-29 | no assertion criteria provided | clinical testing | The CEP290 c.1403G>A variant is predicted to result in the amino acid substitution p.Cys468Tyr. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.016% of alleles in individuals of South Asian descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |