Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000674452 | SCV000799790 | likely pathogenic | Tyrosinemia type I | 2018-05-10 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000674452 | SCV001592922 | pathogenic | Tyrosinemia type I | 2020-03-04 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in FAH are known to be pathogenic (PMID: 9101289, 9633815). 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. Disruption of this splice site has been observed in individual(s) with tyrosinemia type I (PMID: 23000314). ClinVar contains an entry for this variant (Variation ID: 558219). This variant is not present in population databases (ExAC no frequency). This sequence change affects an acceptor splice site in intron 12 of the FAH gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. |