Pathogenic, criteria provided, single submitter | clinical testing | Mendelics | Nov 05, 2018 | - - |
Pathogenic, criteria provided, single submitter | curation | CFTR-France | Jan 29, 2018 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 17, 2022 | The p.R764* pathogenic mutation (also known as c.2290C>T), located in coding exon 14 of the CFTR gene, results from a C to T substitution at nucleotide position 2290. This changes the amino acid from an arginine to a stop codon within coding exon 14. In one study, this mutation was described in 3 individuals with classic cystic fibrosis; one individual was homozygous for this alteration (Strandvik B et al. Genet. Test., 2001;5:235-42). This pathogenic mutation is associated with elevated sweat chloride levels and pancreatic insufficiency (Sosnay PR et al. Nat. Genet., 2013 Oct;45:1160-7). 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. - |
Pathogenic, criteria provided, single submitter | clinical testing | Myriad Genetics, Inc. | Dec 09, 2019 | NM_000492.3(CFTR):c.2290C>T(R764*) is classified as pathogenic in the context of cystic fibrosis and is associated with the classic form of disease. Sources cited for classification include the following: PMID 8956039 and 23974870. Classification of NM_000492.3(CFTR):c.2290C>T(R764*) is based on the following criteria: The variant causes a premature termination codon that is expected to be targeted by nonsense-mediated mRNA decay and is reported in individuals with the relevant phenotype. Please note: this variant was assessed in the context of healthy population screening. - |
Pathogenic, reviewed by expert panel | research | CFTR2 | Mar 17, 2017 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Mar 07, 2023 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 53471). This premature translational stop signal has been observed in individual(s) with cystic fibrosis or congenital bilateral absence of the vas deferens (PMID: 8956039, 21097845, 21520337, 23974870, 27086061, 28544683, 28603918). This variant is present in population databases (rs121908810, gnomAD 0.004%). This sequence change creates a premature translational stop signal (p.Arg764*) 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). - |
Pathogenic, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Jan 13, 2020 | Variant summary: CFTR c.2290C>T (p.Arg764X) 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. The variant allele was found at a frequency of 4.4e-06 in 226822 control chromosomes. c.2290C>T has been well reported in the literature in multiple individuals affected with Cystic Fibrosis (example, Hughes_1996, Roth_2011, Sosnay_2013). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in NMRD (nonsense-mediated RNA decay) (Sheridan_2011). Three clinical diagnostic laboratories and one expert panel (CFTR2) have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. - |