Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000651472 | SCV000773324 | uncertain significance | Xeroderma pigmentosum, group F; Cockayne syndrome; Fanconi anemia complementation group Q | 2024-01-04 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 87 of the ERCC4 protein (p.Arg87His). This variant is present in population databases (rs371487368, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with ERCC4-related conditions. ClinVar contains an entry for this variant (Variation ID: 541246). 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 with a negative predictive value of 80%. 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 | RCV002531974 | SCV003719777 | uncertain significance | Inborn genetic diseases | 2021-09-01 | criteria provided, single submitter | clinical testing | The c.260G>A (p.R87H) alteration is located in exon 2 (coding exon 2) of the ERCC4 gene. This alteration results from a G to A substitution at nucleotide position 260, causing the arginine (R) at amino acid position 87 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |