Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002561023 | SCV003274251 | uncertain significance | Xeroderma pigmentosum, group F; Cockayne syndrome; Fanconi anemia complementation group Q | 2023-11-02 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 150 of the ERCC4 protein (p.Arg150Cys). This variant is present in population databases (rs145402255, gnomAD 0.003%). This missense change has been observed in individual(s) with hereditary breast and ovarian cancer (PMID: 24027083). ClinVar contains an entry for this variant (Variation ID: 929553). 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 expected to disrupt ERCC4 protein function with a positive predictive value of 80%. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on ERCC4 function (PMID: 24027083). 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. |
| Leiden Open Variation Database | RCV001194775 | SCV001364559 | uncertain significance | not provided | 2014-10-06 | no assertion criteria provided | curation | Curator: Arleen D. Auerbach. Submitter to LOVD: Ana Osorio. |