ClinVar Miner

Submissions for variant NM_000492.4(CFTR):c.4C>T (p.Gln2Ter)

dbSNP: rs397508740
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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CFTR2 RCV000576848 SCV000677621 pathogenic Cystic fibrosis 2017-03-17 reviewed by expert panel research
Mendelics RCV000576848 SCV000886255 pathogenic Cystic fibrosis 2018-11-05 criteria provided, single submitter clinical testing
Johns Hopkins Genomics, Johns Hopkins University RCV000576848 SCV001167222 pathogenic Cystic fibrosis 2019-09-15 criteria provided, single submitter clinical testing Previously reported disease-causing CFTR variant. See www.CFTR2.org for phenotype information.
CFTR-France RCV000576848 SCV001169318 pathogenic Cystic fibrosis 2018-01-29 criteria provided, single submitter curation
Invitae RCV000576848 SCV001590547 pathogenic Cystic fibrosis 2023-01-22 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: 53980). This premature translational stop signal has been observed in individual(s) with CFTR-related conditions (PMID: 7512860). This variant is present in population databases (rs397508740, gnomAD 0.006%). This sequence change creates a premature translational stop signal (p.Gln2*) 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 RCV000576848 SCV002640685 pathogenic Cystic fibrosis 2015-04-20 criteria provided, single submitter clinical testing The p.Q2* mutation (also known as c.4C>T) located in coding exon 1 of the CFTR gene, results from a C to T substitution at nucleotide position 4. This changes the amino acid from a glutamine to a stop codon within coding exon 1. The first observation of this mutation was with p.R3W in a Bulgarian patient with lung disease, pancreatic insufficiency and at least one positive sweat test (Savov A 1994, Hum. Mol. Genet.; 3(1):57-60). In addition to the clinical data presented in the literature, since premature stop codons 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, LabCorp RCV000576848 SCV004020682 pathogenic Cystic fibrosis 2023-06-14 criteria provided, single submitter clinical testing Variant summary: CFTR c.4C>T (p.Gln2X) results in a premature termination codon, predicted to cause an absence of the protein due to nonsense mediated decay, which is a commonly known mechanism for disease. The variant allele was found at a frequency of 4e-06 in 251152 control chromosomes. c.4C>T has been reported in the literature in individuals affected with Cystic Fibrosis (example, Savov_1994, Alonso_2007, Alper_2004, Trujillano_2013, Bresnick_2021). These data indicate that the variant is likely to be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 17331079, 15365999, 34857524, 7512860, 23687349). Multiple clinical diagnostic laboratories and databases have submitted 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 RCV003474606 SCV004213507 pathogenic Bronchiectasis with or without elevated sweat chloride 1 2023-05-12 criteria provided, single submitter clinical testing
ClinVar Staff, National Center for Biotechnology Information (NCBI) RCV000576848 SCV000679499 not provided Cystic fibrosis no assertion provided literature only
Natera, Inc. RCV000576848 SCV001464063 pathogenic Cystic fibrosis 2020-09-16 no assertion criteria provided clinical testing

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