Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000227720 | SCV000285542 | uncertain significance | Werner syndrome | 2023-05-21 | criteria provided, single submitter | clinical testing | 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: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The isoleucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 238142). This variant has not been reported in the literature in individuals affected with WRN-related conditions. This variant is present in population databases (rs776463866, gnomAD 0.01%). This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 866 of the WRN protein (p.Val866Ile). |
Gene |
RCV001770192 | SCV001993032 | uncertain significance | not provided | 2019-07-03 | criteria provided, single submitter | clinical testing | In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |