Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000317388 | SCV000330171 | pathogenic | not provided | 2016-01-21 | criteria provided, single submitter | clinical testing | The c.1278+1G>A pathogenic variant in the TCOF1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This splice site variant destroys the canonical splice donor site in intron 9. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. The c.1278+1G>A variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret c.1278+1G>A as a pathogenic variant. |
Labcorp Genetics |
RCV000821693 | SCV000962462 | pathogenic | Treacher Collins syndrome 1 | 2018-10-08 | 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 TCOF1 are known to be pathogenic (PMID: 8894686, 22317976). 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. This variant has been observed in an individual affected with Treacher Collins syndrome (Invitae). ClinVar contains an entry for this variant (Variation ID: 280270). This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 9 of the TCOF1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. |