Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000506324 | SCV000601046 | pathogenic | not provided | 2020-10-14 | criteria provided, single submitter | clinical testing | This frameshift variant causes the premature termination of CFTR protein synthesis. This variant has been reported in an individual with a clinical diagnosis of Cystic Fibrosis (CFMD (http://www.genet.sickkids.on.ca/)). To the best of our knowledge, the variant has not been reported in the published literature. The frequency of this variant in the general population is consistent with pathogenicity. Based on the available information, the variant is classified as pathogenic. |
| Baylor Genetics | RCV001004454 | SCV001163499 | likely pathogenic | Cystic fibrosis; Congenital bilateral aplasia of vas deferens from CFTR mutation | criteria provided, single submitter | clinical testing | ||
| Labcorp Genetics |
RCV001865649 | SCV002245866 | pathogenic | Cystic fibrosis | 2023-03-07 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 439054). This variant has not been reported in the literature in individuals affected with CFTR-related conditions. This variant is present in population databases (rs775663783, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Phe490Serfs*37) in the CFTR gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CFTR are known to be pathogenic (PMID: 1695717, 7691345, 9725922). |
| Ambry Genetics | RCV001865649 | SCV002701267 | pathogenic | Cystic fibrosis | 2014-07-15 | criteria provided, single submitter | clinical testing | The c.1469delT pathogenic mutation, located in coding exon 11 of the CFTR gene, results from a deletion of one nucleotide at nucleotide position 1469, causing a translational frameshift with a predicted alternate stop codon (p.F490Sfs*37). Since frameshifts are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001865649 | SCV004039268 | pathogenic | Cystic fibrosis | 2023-08-24 | criteria provided, single submitter | clinical testing | Variant summary: CFTR c.1469delT (p.Phe490SerfsX37) 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. Variants downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 4e-06 in 251354 control chromosomes. c.1469delT has been reported in the literature in individuals affected with Cystic Fibrosis (Ahmed_2021). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 34949574). Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Baylor Genetics | RCV003476204 | SCV004213264 | likely pathogenic | Bronchiectasis with or without elevated sweat chloride 1 | 2023-10-27 | criteria provided, single submitter | clinical testing |