Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000477187 | SCV000541443 | uncertain significance | Werner syndrome | 2022-10-05 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 502 of the WRN protein (p.Gly502Val). This variant is present in population databases (rs201172985, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with WRN-related conditions. ClinVar contains an entry for this variant (Variation ID: 404021). 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"). 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. |
Ambry Genetics | RCV002522762 | SCV003745161 | uncertain significance | Inborn genetic diseases | 2022-07-20 | criteria provided, single submitter | clinical testing | The c.1505G>T (p.G502V) alteration is located in exon 12 (coding exon 11) of the WRN gene. This alteration results from a G to T substitution at nucleotide position 1505, causing the glycine (G) at amino acid position 502 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Prevention |
RCV003970271 | SCV004777899 | uncertain significance | WRN-related condition | 2024-01-02 | criteria provided, single submitter | clinical testing | The WRN c.1505G>T variant is predicted to result in the amino acid substitution p.Gly502Val. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0026% of alleles in individuals of European (Non-Finnish) descent in gnomAD and has been reported in ClinVar as uncertain (https://www.ncbi.nlm.nih.gov/clinvar/variation/404021/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |