Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000169327 | SCV000220662 | likely pathogenic | Wilson disease | 2014-09-02 | criteria provided, single submitter | literature only | |
Invitae | RCV000169327 | SCV001229833 | pathogenic | Wilson disease | 2019-05-30 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 14 of the ATP7B gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in combination with another ATP7B variant in individuals affected with Wilson disease (PMID: 21796144, 29356957). ClinVar contains an entry for this variant (Variation ID: 188953). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. 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. |