Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV001285544 | SCV001471998 | uncertain significance | Wilson disease | 2020-06-28 | criteria provided, single submitter | clinical testing | The ATP7B c.2231C>T; p.Ser744Phe is reported in the literature in one individual with a clinical diagnosis of Wilson disease (Hua 2016). Additionally, another variant in this codon (c.2230T>C; p.Ser744Pro) has been reported in the homozygous state in an individual with Wilson disease (Curtis 1999). This variant is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. The serine at codon 744 is highly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Due to limited information, the clinical significance of the p.Ser744Phe variant is uncertain at this time. References: Curtis D et al. A study of Wilson disease mutations in Britain. Hum Mutat. 1999;14(4):304-311 Hua R et al. Mutational analysis of ATP7B in Chinese Wilson disease patients. Am J Transl Res. 2016;8(6):2851-2861. |
| Labcorp Genetics |
RCV001285544 | SCV004296491 | pathogenic | Wilson disease | 2023-09-28 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Ser744 amino acid residue in ATP7B. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10502777, 14748773, 21682854). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 ATP7B protein function. ClinVar contains an entry for this variant (Variation ID: 993705). This missense change has been observed in individual(s) with Wilson disease (PMID: 27398169). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 744 of the ATP7B protein (p.Ser744Phe). |