Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001061106 | SCV001225838 | uncertain significance | Werner syndrome | 2023-09-01 | 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: 855771). This variant has not been reported in the literature in individuals affected with WRN-related conditions. This variant is present in population databases (rs555281600, gnomAD 0.002%). This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 776 of the WRN protein (p.Met776Ile). |
Ambry Genetics | RCV003243453 | SCV003944234 | uncertain significance | Inborn genetic diseases | 2023-06-06 | criteria provided, single submitter | clinical testing | The c.2328G>A (p.M776I) alteration is located in exon 20 (coding exon 19) of the WRN gene. This alteration results from a G to A substitution at nucleotide position 2328, causing the methionine (M) at amino acid position 776 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |