Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000540788 | SCV000631782 | uncertain significance | Alstrom syndrome | 2017-04-27 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine with serine at codon 1440 of the ALMS1 protein (p.Tyr1440Ser). The tyrosine residue is moderately conserved and there is a large physicochemical difference between tyrosine and serine. This variant is present in population databases (rs201971114, ExAC 0.1%) but has not been reported in the literature in individuals with a ALMS1-related disease. 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 serine 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. In summary, this variant is a rare missense change that is not predicted to affect protein function, and is found in the population at an appreciable frequency. This variant is not anticipated to cause disease; however, the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. |