Total submissions: 19
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
CFTR2 | RCV000007554 | SCV000071465 | pathogenic | Cystic fibrosis | 2017-03-17 | reviewed by expert panel | research | |
Eurofins Ntd Llc |
RCV000723429 | SCV000232558 | pathogenic | not provided | 2014-07-10 | criteria provided, single submitter | clinical testing | |
Hudson |
RCV000007554 | SCV000584078 | pathogenic | Cystic fibrosis | 2015-06-01 | criteria provided, single submitter | research | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000780169 | SCV000917217 | pathogenic | not specified | 2017-12-15 | criteria provided, single submitter | clinical testing | Variant summary: The CFTR c.1021_1022dupTC (p.Phe342HisfsX28) variant results in a premature termination codon, predicted to cause a truncated or absent CFTR 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 (e.g.c.1155_1156dupTA/p.Asn386fsX3, c.1327_1330dupGATA/p.Ile444fsX3). One in silico tool predicts a damaging outcome for this variant. This variant was found in 9/246180 control chromosomes at a frequency of 0.0000366, which does not exceed the estimated maximal expected allele frequency of a pathogenic CFTR variant (0.0129603). This variant has been reported in numerous CF patients (Iannuzzi_1991, Friedman_1995, Ahmed_2003, Sosnay_2013). In addition, multiple clinical diagnostic laboratories/reputable databases, including CFTR2, classified this variant as pathogenic. Taken together, this variant is classified as pathogenic. |
Baylor Genetics | RCV001004249 | SCV001163125 | pathogenic | Cystic fibrosis; Congenital bilateral aplasia of vas deferens from CFTR mutation | criteria provided, single submitter | clinical testing | ||
Clinical Genetics and Genomics, |
RCV000723429 | SCV001450366 | pathogenic | not provided | 2017-06-15 | criteria provided, single submitter | clinical testing | |
Johns Hopkins Genomics, |
RCV000007554 | SCV001573148 | pathogenic | Cystic fibrosis | 2021-04-23 | criteria provided, single submitter | clinical testing | Disease-causing CFTR variant. See www.CFTR2.org for phenotype information. |
Labcorp Genetics |
RCV000007554 | SCV001590784 | pathogenic | Cystic fibrosis | 2023-09-10 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 7134). For these reasons, this variant has been classified as Pathogenic. This variant is also known as 1154insTC. This premature translational stop signal has been observed in individuals with Cystic Fibrosis (CF) (PMID: 1990834, 12865275, 23974870; Invitae). This variant is present in population databases (rs751437088, gnomAD 0.006%). This sequence change creates a premature translational stop signal (p.Phe342Hisfs*28) 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). |
Mayo Clinic Laboratories, |
RCV000723429 | SCV001714228 | pathogenic | not provided | 2022-06-28 | criteria provided, single submitter | clinical testing | PP5, PM2, PVS1 |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000723429 | SCV002046184 | pathogenic | not provided | 2021-02-09 | criteria provided, single submitter | clinical testing | This frameshift variant causes the premature termination of CFTR protein synthesis. In addition, it has been reported in individuals affected with Cystic Fibrosis in the published literature (PMID: 7550243 (1995), 26708955 (2016), 23974870 (2013), 22658665 (2012), 1990834 (1991), 12865275 (2003)). Therefore, the variant is classified as pathogenic. |
Genome Diagnostics Laboratory, |
RCV000007554 | SCV002507319 | pathogenic | Cystic fibrosis | 2019-07-09 | criteria provided, single submitter | clinical testing | |
Institute of Human Genetics, |
RCV000007554 | SCV002573797 | 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 |
Ambry Genetics | RCV000007554 | SCV002673850 | pathogenic | Cystic fibrosis | 2021-12-01 | criteria provided, single submitter | clinical testing | The c.1021_1022dupTC pathogenic mutation, located in coding exon 8 of the CFTR gene, results from a duplication of TC at nucleotide position 1021, causing a translational frameshift with a predicted alternate stop codon (p.F342Hfs*28). This pathogenic mutation was reported to account for 0.5% of 1,238 predominantly American Caucasian cystic fibrosis (CF) chromosomes (Friedman KJ et al. Hum. Mutat., 1995;6:95-6). In another study, this mutation was reportedly detected in trans with p.F508del in two unrelated individuals with elevated sweat chloride levels, pancreatic insufficiency, and poor growth (Alper OM et al. Am. J. Med. Genet. A, 2003 Jul;120A:294-5). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Of note, this alteration is also known as c.1154_1155insTC, 1154insTC, and c.1022_1023insTC in published literature. 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. |
Baylor Genetics | RCV003473014 | SCV004213254 | pathogenic | Bronchiectasis with or without elevated sweat chloride 1 | 2024-03-04 | criteria provided, single submitter | clinical testing | |
OMIM | RCV000007554 | SCV000027755 | pathogenic | Cystic fibrosis | 2003-07-15 | no assertion criteria provided | literature only | |
Counsyl | RCV000007554 | SCV000220355 | pathogenic | Cystic fibrosis | 2015-10-09 | no assertion criteria provided | clinical testing | |
Natera, |
RCV001831528 | SCV002078182 | pathogenic | CFTR-related disorder | 2017-03-17 | no assertion criteria provided | clinical testing | |
Genome Diagnostics Laboratory, |
RCV001831528 | SCV002507403 | pathogenic | CFTR-related disorder | 2019-07-09 | no assertion criteria provided | clinical testing | |
Prevention |
RCV001831528 | SCV004112652 | pathogenic | CFTR-related disorder | 2024-07-24 | no assertion criteria provided | clinical testing | The CFTR c.1021_1022dupTC variant is predicted to result in a frameshift and premature protein termination (p.Phe342Hisfs*28). This variant has been reported to be causative for cystic fibrosis and cystic fibrosis with pancreatic insufficiency (reported as c.1154insTC, Iannuzzi et al., 1991. PubMed ID: 1990834; Table S2, Sosnay et al. 2013. PubMed ID: 23974870; Ooi and Durie. 2012. PubMed ID: 22658665). Frameshift variants in CFTR are expected to be pathogenic. This variant is interpreted as pathogenic. |