Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000686451 | SCV000813970 | uncertain significance | Werner syndrome | 2022-10-24 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 515 of the WRN protein (p.Glu515Gln). This variant is not present in population databases (gnomAD no frequency). 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: 566600). 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 | RCV002544750 | SCV003586871 | uncertain significance | Inborn genetic diseases | 2022-04-07 | criteria provided, single submitter | clinical testing | The c.1543G>C (p.E515Q) alteration is located in exon 12 (coding exon 11) of the WRN gene. This alteration results from a G to C substitution at nucleotide position 1543, causing the glutamic acid (E) at amino acid position 515 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |