Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000004054 | SCV000220772 | likely pathogenic | Wilson disease | 2014-10-09 | criteria provided, single submitter | literature only | |
| Integrated Genetics/Laboratory Corporation of America | RCV000004054 | SCV000918604 | pathogenic | Wilson disease | 2018-07-23 | criteria provided, single submitter | clinical testing | Variant summary: ATP7B c.1708-1G>C is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Five predict the variant abolishes a 3' acceptor site. At least one publication reports experimental evidence that this variant determines exon 5 skipping (Tsai_1999). The variant allele was found at a frequency of 2.9e-05 in 277094 control chromosomes (gnomAD). The variant, c.1708-1G>C, has been reported in the literature in multiple individuals affected with Wilson Disease (Coffey_2013, Hua_2016, Mukherjee_2014, Tsai_1999). These data indicate that the variant is very likely to be associated with disease. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Baylor Genetics | RCV000004054 | SCV001163737 | pathogenic | Wilson disease | criteria provided, single submitter | clinical testing | ||
| Invitae | RCV000004054 | SCV001227124 | pathogenic | Wilson disease | 2019-02-15 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 4 of the ATP7B gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is present in population databases (rs137853280, ExAC 0.02%). This variant has been observed in several individuals affected with Wilson disease (PMID: 7626145, 27398169, 9829905). This variant is also known in the literature as c.1711-1G>C. ClinVar contains an entry for this variant (Variation ID: 3850). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in ATP7B are known to be pathogenic (PMID: 10441329, 16283883). For these reasons, this variant has been classified as Pathogenic. |
| OMIM | RCV000004054 | SCV000024220 | pathogenic | Wilson disease | 2000-11-01 | no assertion criteria provided | literature only |