Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001227574 | SCV001399936 | uncertain significance | Xeroderma pigmentosum, group F; Cockayne syndrome; Fanconi anemia complementation group Q | 2022-12-13 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 455 of the ERCC4 protein (p.Lys455Arg). This variant is present in population databases (rs759312308, gnomAD 0.007%). 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ERCC4 protein function. ClinVar contains an entry for this variant (Variation ID: 955014). This variant has not been reported in the literature in individuals affected with ERCC4-related conditions. |