Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000409393 | SCV000486347 | likely pathogenic | Cystic fibrosis | 2016-05-13 | criteria provided, single submitter | clinical testing | |
| Mendelics | RCV000409393 | SCV000886305 | pathogenic | Cystic fibrosis | 2018-11-05 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000409393 | SCV001578292 | pathogenic | Cystic fibrosis | 2020-03-02 | criteria provided, single submitter | clinical testing | 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 congenital bilateral absence of the vas deferens (PMID: 22483971). ClinVar contains an entry for this variant (Variation ID: 370916). This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 9 of the CFTR gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in CFTR are known to be pathogenic (PMID: 1695717, 7691345, 9725922). For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV000409393 | SCV002651619 | likely pathogenic | Cystic fibrosis | 2017-05-02 | criteria provided, single submitter | clinical testing | The c.1209+1G>T intronic variant results from a G to T substitution one nucleotide after coding exon 9 of the CFTR gene. This nucleotide position is highly conserved in available vertebrate species. This alteration is predicted to abolish the native donor site using the ESEfinder in silico model; however experimental evidence is not currently available. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as likely pathogenic. |
| Baylor Genetics | RCV003475957 | SCV004213558 | likely pathogenic | Bronchiectasis with or without elevated sweat chloride 1 | 2023-02-23 | criteria provided, single submitter | clinical testing |