Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000530203 | SCV000629689 | uncertain significance | Werner syndrome | 2023-03-20 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with WRN-related conditions. 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 alanine 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: 458453). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 1140 of the WRN protein (p.Ser1140Ala). |
| Ambry Genetics | RCV002527686 | SCV003739812 | uncertain significance | Inborn genetic diseases | 2022-03-29 | criteria provided, single submitter | clinical testing | The c.3418T>G (p.S1140A) alteration is located in exon 29 (coding exon 28) of the WRN gene. This alteration results from a T to G substitution at nucleotide position 3418, causing the serine (S) at amino acid position 1140 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |