Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001049557 | SCV001213613 | uncertain significance | Werner syndrome | 2022-05-14 | 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. Studies have shown that this missense change is associated with altered splicing resulting in unknown protein product impact (Invitae). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available"). ClinVar contains an entry for this variant (Variation ID: 846289). This variant has not been reported in the literature in individuals affected with WRN-related conditions. This variant is present in population databases (rs369158322, gnomAD 0.007%). This sequence change replaces glutamine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 1229 of the WRN protein (p.Gln1229Pro). |