ClinVar Miner

Submissions for variant NM_000492.4(CFTR):c.1021_1022dup (p.Phe342fs)

dbSNP: rs387906360
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Total submissions: 19
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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 (ga) RCV000723429 SCV000232558 pathogenic not provided 2014-07-10 criteria provided, single submitter clinical testing
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology RCV000007554 SCV000584078 pathogenic Cystic fibrosis 2015-06-01 criteria provided, single submitter research
Women's Health and Genetics/Laboratory Corporation of America, LabCorp 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, Karolinska University Hospital RCV000723429 SCV001450366 pathogenic not provided 2017-06-15 criteria provided, single submitter clinical testing
Johns Hopkins Genomics, Johns Hopkins University 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 (formerly Invitae), Labcorp 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, Mayo Clinic 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, The Hospital for Sick Children RCV000007554 SCV002507319 pathogenic Cystic fibrosis 2019-07-09 criteria provided, single submitter clinical testing
Institute of Human Genetics, University of Leipzig Medical Center 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, Inc. RCV001831528 SCV002078182 pathogenic CFTR-related disorder 2017-03-17 no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV001831528 SCV002507403 pathogenic CFTR-related disorder 2019-07-09 no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences 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.

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