Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| CFTR2 | RCV000056390 | SCV000071485 | pathogenic | Cystic fibrosis | 2017-03-17 | reviewed by expert panel | research | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000056390 | SCV000697005 | pathogenic | Cystic fibrosis | 2020-08-31 | criteria provided, single submitter | clinical testing | Variant summary: CFTR c.4077_4080delinsAA (p.Val1360ThrfsX3) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251266 control chromosomes. c.4077_4080delinsAA has been reported in the literature in multiple individuals affected with Cystic Fibrosis (examples- Sosnay_2013). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One expert panel has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and cited the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Baylor Genetics | RCV001004515 | SCV001163560 | pathogenic | Cystic fibrosis; Congenital bilateral aplasia of vas deferens from CFTR mutation | criteria provided, single submitter | clinical testing | ||
| Johns Hopkins Genomics, |
RCV000056390 | SCV002570379 | pathogenic | Cystic fibrosis | 2022-07-23 | criteria provided, single submitter | clinical testing | Disease-causing CFTR variant. See www.CFTR2.org for phenotype information. |
| Ambry Genetics | RCV000056390 | SCV002628211 | pathogenic | Cystic fibrosis | 2023-08-09 | criteria provided, single submitter | clinical testing | The c.4077_4080delTGTTinsAA pathogenic mutation, located in coding exon 25 of the CFTR gene, results from the deletion of 4 nucleotides and insertion of two nucleotides causing a translational frameshift with a predicted alternate stop codon (p.V1360Tfs*3). This mutation is associated with elevated sweat chloride levels, decreased lung function, and pancreatic insufficiency (Sosnay PR et al. Nat. Genet., 2013 Oct;45:1160-7). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
| Prevention |
RCV004537231 | SCV004115904 | pathogenic | CFTR-related disorder | 2022-10-05 | criteria provided, single submitter | clinical testing | The CFTR c.4077_4080delinsAA variant is predicted to result in a frameshift and premature protein termination (p.Val1360Thrfs*3). This variant has been reported in individuals with cystic fibrosis and individuals undergoing carrier screening for cystic fibrosis (Table S2, Sosnay et al. 2013. PubMed ID: 23974870; Table S3, Beauchamp. 2019. PubMed ID: 31036917). (Table S2, Sosnay et al. 2013. PubMed ID: 23974870; Table S3, Beauchamp. 2019. PubMed ID: 31036917). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Frameshift variants in CFTR are expected to be pathogenic. This variant is interpreted as pathogenic. |
| Counsyl | RCV000056390 | SCV001132352 | likely pathogenic | Cystic fibrosis | 2014-01-02 | no assertion criteria provided | clinical testing |