Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Broad Center for Mendelian Genomics, |
RCV001248953 | SCV001422734 | uncertain significance | not specified | 2020-01-22 | criteria provided, single submitter | curation | The p.Tyr1424Cys variant in ATP7B has not been previously reported in individuals with Wilson Disease but has been identified in 0.01650% (4/24238) of African chromosomes and 0.001557% (2/128452) of European (non-Finnish) chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs372435824). Although this variant has been seen in the general population, its frequency is not high enough to rule out a pathogenic role. Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the p.Tyr1424Cys variant is uncertain. ACMG/AMP Criteria applied: None (Richards 2015). |
Invitae | RCV001879745 | SCV002155145 | uncertain significance | Wilson disease | 2022-08-03 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 1424 of the ATP7B protein (p.Tyr1424Cys). This variant is present in population databases (rs372435824, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with ATP7B-related conditions. ClinVar contains an entry for this variant (Variation ID: 972771). 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 ATP7B protein function. 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. |
Fulgent Genetics, |
RCV001879745 | SCV002788463 | uncertain significance | Wilson disease | 2021-11-17 | criteria provided, single submitter | clinical testing |