Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001337185 | SCV001530776 | uncertain significance | Senior-Loken syndrome 7; Bardet-Biedl syndrome 16 | 2020-08-25 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with SDCCAG8-related conditions. This variant is present in population databases (rs752002252, ExAC 0.01%). This sequence change replaces methionine with valine at codon 408 of the SDCCAG8 protein (p.Met408Val). The methionine residue is moderately conserved and there is a small physicochemical difference between methionine and valine. 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 valine 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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. |