Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001069289 | SCV001234446 | uncertain significance | Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis | 2019-11-23 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The isoleucine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with CEP290-related conditions. This sequence change replaces threonine with isoleucine at codon 1938 of the CEP290 protein (p.Thr1938Ile). The threonine residue is moderately conserved and there is a moderate physicochemical difference between threonine and isoleucine. |
| Prevention |
RCV004726866 | SCV005338686 | uncertain significance | CEP290-related disorder | 2024-06-26 | no assertion criteria provided | clinical testing | The CEP290 c.5813C>T variant is predicted to result in the amino acid substitution p.Thr1938Ile. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |