Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| CFTR2 | RCV000007597 | SCV000245897 | pathogenic | Cystic fibrosis | 2017-03-17 | reviewed by expert panel | research | |
| North West Genomic Laboratory Hub, |
RCV003996079 | SCV004814222 | pathogenic | Cystic fibrosis; Hereditary pancreatitis | 2020-04-20 | criteria provided, single submitter | clinical testing | Criteria Codes: PM2 PVS1 PM3_Str |
| Ambry Genetics | RCV000007597 | SCV002623119 | pathogenic | Cystic fibrosis | 2022-08-17 | criteria provided, single submitter | clinical testing | The c.3718-1G>A intronic pathogenic mutation results from a G to A substitution one nucleotide upstream from coding exon 23 of the CFTR gene. Alterations that disrupt the canonical splice site are expected to result in aberrant splicing. In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site. The resulting transcript is predicted to be in-frame and is not expected to trigger nonsense-mediated mRNA decay; however, direct evidence is unavailable. The exact functional effect of the altered amino acid sequence is unknown; however, the impacted region is critical for protein function (Ambry internal data). This variant has been reported in multiple individuals with an elevated sweat chloride level in The Clinical and Functional TRanslation of CFTR (CFTR2) database (available at http://cftr2.org. Accessed 08/17/2022), as well as in individuals with cystic fibrosis or CFTR-related disorders in the literature (Terzic M et al. Balkan J Med Genet, 2019 Jun;22:35-40; Audrézet MP et al. Hum Mol Genet, 1993 Jan;2:51-4). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000007597 | SCV001467947 | pathogenic | Cystic fibrosis | 2020-12-11 | criteria provided, single submitter | clinical testing | Variant summary: CFTR c.3718-1G>A 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: Four predict the variant abolishes a 3' acceptor site. Two predict the variant creates a new 3' acceptor site. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 250942 control chromosomes. c.3718-1G>A has been reported in the literature in individuals affected with Cystic Fibrosis (example, Audrezet_1993, Terzic_2019). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories and one expert panel (CFTR2) have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All submitters classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| CFTR- |
RCV000007597 | SCV001169360 | pathogenic | Cystic fibrosis | 2018-01-29 | criteria provided, single submitter | curation | |
| Natera, |
RCV001831544 | SCV002075874 | pathogenic | CFTR-related disorder | 2017-03-17 | no assertion criteria provided | clinical testing | |
| OMIM | RCV000007597 | SCV000027798 | pathogenic | Cystic fibrosis | 2018-04-09 | no assertion criteria provided | literature only |