Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001922452 | SCV002171036 | uncertain significance | Leber congenital amaurosis 2; Retinitis pigmentosa 20 | 2022-03-10 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 129 of the RPE65 protein (p.Thr129Ile). This variant is present in population databases (rs768336015, gnomAD 0.003%). This missense change has been observed in individuals with RPE65-related conditions (PMID: 31736247; Invitae). 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"). 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. |