Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001339011 | SCV001532724 | uncertain significance | Leber congenital amaurosis 2; Retinitis pigmentosa 20 | 2021-08-27 | criteria provided, single submitter | clinical testing | This variant, c.1443_1445del, results in the deletion of 1 amino acid(s) of the RPE65 protein (p.Glu481del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with inherited retinal dystrophy (PMID: 29332120). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV002265965 | SCV002547976 | uncertain significance | not specified | 2022-05-26 | criteria provided, single submitter | clinical testing | Variant summary: RPE65 c.1443_1445delAGA (p.Glu481del) results in an in-frame deletion that is predicted to remove one amino acid from the encoded protein. The variant allele was found at a frequency of 4e-06 in 250802 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1443_1445delAGA has been reported in the literature in at least one compound heterozygous individual affected with Leber Congenital Amaurosis (Kumaran_2018). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One ClinVar submitter has assessed the variant since 2014: the variant was classified as of uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
Laboratory of Genetics in Ophthalmology, |
RCV001250695 | SCV001425569 | likely pathogenic | Leber congenital amaurosis 2 | no assertion criteria provided | research |