Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000436721 | SCV000520080 | likely benign | not specified | 2015-10-26 | criteria provided, single submitter | clinical testing | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. |
Labcorp Genetics |
RCV001242972 | SCV001416098 | uncertain significance | Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis | 2024-12-16 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 728 of the CEP290 protein (p.Asn728Ser). This variant is present in population databases (rs752513342, gnomAD 0.002%). 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: 381032). 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 |
RCV004532991 | SCV004117996 | uncertain significance | CEP290-related disorder | 2023-08-04 | criteria provided, single submitter | clinical testing | The CEP290 c.2183A>G variant is predicted to result in the amino acid substitution p.Asn728Ser. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0032% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/12-88505505-T-C). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |