Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001035584 | SCV001198917 | uncertain significance | Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis | 2022-08-09 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 751 of the CEP290 protein (p.Arg751Gln). 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 missense change has been observed in individual(s) with non-syndromic retinal dystrophy (PMID: 34196655). ClinVar contains an entry for this variant (Variation ID: 834820). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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 |
RCV004536062 | SCV004115559 | uncertain significance | CEP290-related disorder | 2023-08-14 | criteria provided, single submitter | clinical testing | The CEP290 c.2252G>A variant is predicted to result in the amino acid substitution p.Arg751Gln. This variant has been reported in an individual with nonsyndromic retinal dystrophy (Table 2, Testa et al. 2021. PubMed ID: 34196655). This variant is reported in 0.0012% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/12-88505094-C-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
Natera, |
RCV001827214 | SCV002094296 | uncertain significance | Leber congenital amaurosis | 2021-03-11 | no assertion criteria provided | clinical testing |