Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001215767 | SCV001387529 | uncertain significance | Retinitis pigmentosa 12; Leber congenital amaurosis 8 | 2022-07-29 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 649 of the CRB1 protein (p.Asp649Asn). This variant is present in population databases (rs138936375, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with CRB1-related conditions. ClinVar contains an entry for this variant (Variation ID: 945191). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15". The asparagine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |
Ambry Genetics | RCV004033977 | SCV004852066 | uncertain significance | Inborn genetic diseases | 2021-09-17 | criteria provided, single submitter | clinical testing | The c.1945G>A (p.D649N) alteration is located in exon 6 (coding exon 6) of the CRB1 gene. This alteration results from a G to A substitution at nucleotide position 1945, causing the aspartic acid (D) at amino acid position 649 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Natera, |
RCV001828718 | SCV002090152 | uncertain significance | Leber congenital amaurosis | 2020-09-01 | no assertion criteria provided | clinical testing |