Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001192431 | SCV001360545 | pathogenic | Cystic fibrosis | 2023-05-22 | criteria provided, single submitter | clinical testing | Variant summary: CFTR c.234dupC (p.Trp79LeufsX32) 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. Variants downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 8e-06 in 251016 control chromosomes (gnomAD). c.234dupC has been reported in the literature in at-least one individual affected with Cystic Fibrosis (example, Schrijver_2016) although a different variant, c.234dupT, also translating to the same protein effect has been reported in affected individuals (example, Petrova_2019, Soe_2017). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 26708955, 30548586, 28174639). Three ClinVar submitters (evaluation after 2014) cite this variant as pathogenic (n=2) and likely pathogenic (n=1). Based on the evidence outlined above, the variant was classified as pathogenic. |
Johns Hopkins Genomics, |
RCV001192431 | SCV002051810 | pathogenic | Cystic fibrosis | 2021-09-28 | criteria provided, single submitter | clinical testing | CFTR c.234dupC has been reported in an individual with features of cystic fibrosis. This variant (rs751305135) is rare (<0.1%) in a large population dataset (gnomAD: 2/251016 total alleles; 0.0008%; no homozygotes) and has been reported in ClinVar (variant ID: 928495). This frameshift variant results in a premature stop codon in exon 4 likely leading to nonsense-mediated decay and lack of protein production. We consider this variant to be pathogenic. |
Ambry Genetics | RCV001192431 | SCV002732668 | pathogenic | Cystic fibrosis | 2021-11-04 | criteria provided, single submitter | clinical testing | The c.234dupC pathogenic mutation, located in coding exon 3 of the CFTR gene, results from a duplication of C at nucleotide position 234, causing a translational frameshift with a predicted alternate stop codon (p.W79Lfs*32). This alteration has been detected in individuals with cystic fibrosis or CFTR-related disorders (Schrijver I et al. J Mol Diagn, 2016 Jan;18:39-50). 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. |
Natera, |
RCV001833737 | SCV002080092 | likely pathogenic | CFTR-related disorders | 2020-10-19 | no assertion criteria provided | clinical testing |