Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000478827 | SCV000574077 | uncertain significance | not provided | 2017-11-06 | criteria provided, single submitter | clinical testing | The P90L variant has not been publishedas pathogenic or been reported as benign to our knowledge. It is not observed in large population cohorts (Lek et al.,2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The P90L variant is a semi-conservativeamino acid substitution, which may impact secondary protein structure as these residues differ in some properties.However, this substitution occurs at a position that is not conserved across species, and in silico analysis isinconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Lastly,while some missense variants have been reported in association with Alstrom syndrome, most pathogenic variants inALMS1 reported to date are predicted to cause premature protein truncation (Marshall et al., 2012; Stenson et al.,2014). |
Invitae | RCV000809783 | SCV000949958 | uncertain significance | Alstrom syndrome | 2022-09-30 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 90 of the ALMS1 protein (p.Pro90Leu). This variant is present in population databases (no rsID available, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with ALMS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 424286). 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. |
Natera, |
RCV000809783 | SCV001463495 | uncertain significance | Alstrom syndrome | 2020-01-24 | no assertion criteria provided | clinical testing |