Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000671716 | SCV000796722 | uncertain significance | Wilson disease | 2017-12-28 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002282316 | SCV002572264 | uncertain significance | not specified | 2022-08-03 | criteria provided, single submitter | clinical testing | Variant summary: ATP7B c.1616C>T (p.Pro539Leu) results in a non-conservative amino acid change located in the Heavy metal-associated domain (IPR006121) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 249472 control chromosomes (gnomAD). c.1616C>T has been reported in three Austrian siblings with compound heterozygous genotype c.1616C>T/c.2448G>T diagnosed with Wilson Disease (example: Hofer_2012). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. |
| Baylor Genetics | RCV000671716 | SCV004216299 | likely pathogenic | Wilson disease | 2023-10-10 | criteria provided, single submitter | clinical testing | |
| Fulgent Genetics, |
RCV000671716 | SCV005636245 | likely pathogenic | Wilson disease | 2024-05-14 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000671716 | SCV005835476 | uncertain significance | Wilson disease | 2024-04-06 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 539 of the ATP7B protein (p.Pro539Leu). This variant is present in population databases (rs572122562, gnomAD 0.003%). This missense change has been observed in individual(s) with Wilson disease (PMID: 22763723). ClinVar contains an entry for this variant (Variation ID: 555819). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on 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. |