Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV001001202 | SCV001158362 | pathogenic | not specified | 2019-04-09 | criteria provided, single submitter | clinical testing | The CFTR c.708delT; p.Gln237fs variant, to our knowledge, is not reported in the medical literature but is reported as pathogenic by Emory Genetics Laboratory. This variant is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. This variant causes a frameshift by deleting a single nucleotide, so it is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. CFTR loss-of-function is an established mechanism of disease, and truncating variants downstream of c.708delT are reported in individuals with cystic fibrosis and are considered pathogenic (Schrijver 2005, CFTR2 database). Based on available information, the c.708delT variant is considered to be pathogenic. References: CFTR2 database: https://cftr2.org Schrijver I et al. Diagnostic testing by CFTR gene mutation analysis in a large group of Hispanics: novel mutations and assessment of a population-specific mutation spectrum. J Mol Diagn. 2005 May;7(2):289-99. |
| Institute of Human Genetics, |
RCV002284454 | SCV002574013 | pathogenic | Cystic fibrosis | 2022-09-05 | criteria provided, single submitter | curation | This variant was identified in 2 unrelated patients with a clinically confirmed diagnosis of cystic fibrosis. The variant was classified in the context of a project re-classifying variants in the German Cystic Fibrosis Registry (Muko.e.V.). Link: https://www.muko.info/angebote/qualitaetsmanagement/register/cf-einrichtungen/mukoweb. Criteria applied: PVS1, PM3, PM2_SUP, PP4 |
| Labcorp Genetics |
RCV002284454 | SCV003025307 | pathogenic | Cystic fibrosis | 2022-06-08 | 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: 811381). This variant has not been reported in the literature in individuals affected with CFTR-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln237Argfs*4) 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). |
| Baylor Genetics | RCV004569847 | SCV005057464 | pathogenic | Bronchiectasis with or without elevated sweat chloride 1 | 2023-12-19 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002284454 | SCV005107475 | pathogenic | Cystic fibrosis | 2024-04-04 | criteria provided, single submitter | clinical testing | The c.708delT pathogenic mutation, located in coding exon 6 of the CFTR gene, results from a deletion of one nucleotide at nucleotide position 708, causing a translational frameshift with a predicted alternate stop codon (p.Q237Rfs*4). 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. |