Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001309896 | SCV001499410 | uncertain significance | Cone-rod dystrophy 13; Leber congenital amaurosis 6 | 2020-01-31 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with RPGRIP1-related conditions. This variant is present in population databases (rs766604917, ExAC 0.09%). This sequence change replaces valine with isoleucine at codon 143 of the RPGRIP1 protein (p.Val143Ile). The valine residue is weakly conserved and there is a small physicochemical difference between valine and isoleucine. 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. |