Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000937216 | SCV001082992 | likely benign | Wilson disease | 2024-01-30 | criteria provided, single submitter | clinical testing | |
| Illumina Laboratory Services, |
RCV000937216 | SCV001268807 | uncertain significance | Wilson disease | 2017-04-27 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
| Genome- |
RCV000937216 | SCV001977197 | likely benign | Wilson disease | 2021-08-10 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002298802 | SCV002598864 | uncertain significance | not specified | 2022-09-28 | criteria provided, single submitter | clinical testing | Variant summary: ATP7B c.406A>G (p.Arg136Gly) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00031 in 249348 control chromosomes (gnomAD), predominantly at a frequency of 0.0025 within the South Asian subpopulation in the gnomAD database. This frequency is not significantly higher than expected for a pathogenic variant in ATP7B causing Wilson Disease (0.00031 vs 0.0054), allowing no conclusion about variant significance. c.406A>G has been reported in the literature in individuals affected with Wilson Disease (Mukherjee_2014), Bipolar Disorder (Sriretnakumar_2019) and Neuroinflammation (McCreary_2019). These reports do not provide unequivocal conclusions about association of the variant with Wilson Disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three ClinVar submitters have assessed the variant since 2014: one classified the variant as uncertain significance and two as likely benign. Based on the evidence outlined above, the variant was classified as uncertain significance. |