Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000814173 | SCV000954574 | uncertain significance | Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis | 2021-08-27 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine with valine at codon 1743 of the CEP290 protein (p.Ala1743Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with CEP290-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. |
Fulgent Genetics, |
RCV002495144 | SCV002798256 | uncertain significance | Leber congenital amaurosis 10; Meckel syndrome, type 4; Senior-Loken syndrome 6; Joubert syndrome 5; Bardet-Biedl syndrome 14 | 2022-01-26 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV001830781 | SCV002094199 | uncertain significance | Leber congenital amaurosis | 2020-02-10 | no assertion criteria provided | clinical testing | |
Prevention |
RCV004538118 | SCV004712858 | uncertain significance | CEP290-related disorder | 2024-02-14 | no assertion criteria provided | clinical testing | The CEP290 c.5228C>T variant is predicted to result in the amino acid substitution p.Ala1743Val. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.00097% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |