Total submissions: 13
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| CFTR2 | RCV000056401 | SCV000071544 | pathogenic | Cystic fibrosis | 2017-03-17 | reviewed by expert panel | research | |
| Johns Hopkins Genomics, |
RCV000056401 | SCV004239101 | pathogenic | Cystic fibrosis | 2023-07-26 | criteria provided, single submitter | clinical testing | Disease-causing CFTR variant. See www.CFTR2.org for phenotype information. |
| Baylor Genetics | RCV003474614 | SCV004213313 | pathogenic | Bronchiectasis with or without elevated sweat chloride 1 | 2024-02-22 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV000056401 | SCV002664680 | pathogenic | Cystic fibrosis | 2025-09-28 | criteria provided, single submitter | clinical testing | The p.Q220* pathogenic mutation (also known as c.658C>T), located in coding exon 6 of the CFTR gene, results from a C to T substitution at nucleotide position 658. This changes the amino acid from a glutamine to a stop codon within coding exon 6. This mutation was described in trans with a second pathogenic mutation in an individual presenting with respiratory symptoms, bronchiectasis, and elevated sweat chloride levels (Koh WJ et al. J Korean Med Sci. 2006;21(3):563-6). In addition to pulmonary symptoms and elevated sweat chloride levels, this mutation is also associated with pancreatic insufficiency (Sosnay PR et al. Nat Genet. 2013;45(10):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. |
| Institute of Human Genetics, |
RCV000056401 | SCV002573890 | pathogenic | Cystic fibrosis | 2022-09-05 | criteria provided, single submitter | curation | This variant was identified in 1 patient 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, PM2_SUP, PM3_VSTR, PP4 |
| Natera, |
RCV001826695 | SCV002078124 | pathogenic | CFTR-related disorder | 2025-10-16 | criteria provided, single submitter | clinical testing | The c.658C>T variant in CFTR is a nonsense variant predicted to introduce a stop codon at amino acid 220. This variant is expected to result in nonsense mediated decay, truncation, or a dysfunctional protein product. This variant is rare in the general population with a frequency below the threshold expected for the associated phenotype(s). This variant has been observed in one or more individuals affected with the associated recessive disease, as either homozygous or compound heterozygous with a second variant (PMID: 16778407). Given the available evidence, this variant is classified as Pathogenic. |
| Labcorp Genetics |
RCV000056401 | SCV001580630 | pathogenic | Cystic fibrosis | 2025-10-18 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln220*) 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). This variant is present in population databases (rs397508778, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with clinical features of cystic fibrosis (PMID: 7515303, 16778407). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 54036). For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000056401 | SCV001362674 | pathogenic | Cystic fibrosis | 2019-05-28 | criteria provided, single submitter | clinical testing | Variant summary: CFTR c.658C>T (p.Gln220X) 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 (c.803delA, p.Asn268fsX17; c.850dupA, p.Met284fsX3; c.948delT, p.Phe316LeufsX12). The variant allele was found at a frequency of 4e-06 in 251438 control chromosomes (gnomAD). The variant, c.658C>T, has been reported in the literature in multiple individuals affected with Cystic Fibrosis (Koh_2006, Tomaiuolo_2010, Ooi_2012, Sosonay_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 publication, Sosnay_2013, reports that spliced RNA product is less than 10% of WT level predicted by NMD (nonsense mediated decay). Three ClinVar submissions including one expert panel (CFTR2) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| CFTR- |
RCV000056401 | SCV001169335 | pathogenic | Cystic fibrosis | 2018-01-29 | criteria provided, single submitter | curation | |
| Baylor Genetics | RCV001004236 | SCV001163112 | pathogenic | Cystic fibrosis; Congenital bilateral aplasia of vas deferens from CFTR mutation | criteria provided, single submitter | clinical testing | ||
| Fulgent Genetics, |
RCV000763566 | SCV000894405 | pathogenic | Bronchiectasis with or without elevated sweat chloride 1; Cystic fibrosis; Hereditary pancreatitis; Congenital bilateral aplasia of vas deferens from CFTR mutation | 2018-10-31 | criteria provided, single submitter | clinical testing | |
| Mendelics | RCV000056401 | SCV000886230 | pathogenic | Cystic fibrosis | 2018-11-05 | criteria provided, single submitter | clinical testing | |
| Counsyl | RCV000056401 | SCV001132351 | pathogenic | Cystic fibrosis | 2014-01-02 | no assertion criteria provided | clinical testing | This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact variantquestions@myriad.com. |