Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| CFTR2 | RCV000666972 | SCV001981595 | pathogenic | Cystic fibrosis | 2020-01-10 | reviewed by expert panel | research | |
| Counsyl | RCV000666972 | SCV000791353 | uncertain significance | Cystic fibrosis | 2017-05-15 | criteria provided, single submitter | clinical testing | |
| Institute of Human Genetics, |
RCV000666972 | SCV002573950 | pathogenic | Cystic fibrosis | 2022-09-05 | criteria provided, single submitter | curation | This variant was identified in 2 unrelated patients 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: PM2_SUP, PM3_STR, PM5_STR, PP3 |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000666972 | SCV004028736 | likely pathogenic | Cystic fibrosis | 2023-07-18 | criteria provided, single submitter | clinical testing | Variant summary: CFTR c.4097T>A (p.Ile1366Asn) results in a non-conservative amino acid change located in the ATP-binding domain (IPR003439) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251286 control chromosomes (i.e., 1 heterozygote; gnomAD v2.1 Exomes dataset). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.4097T>A has been reported in the literature in at least two compound heterozygous individuals affected with Cystic Fibrosis (e.g., Krenkova_2012, Levy_2016, Geurts_2020, Raraigh_2022). These data indicate that the variant is likely to be associated with disease. At least one unpublished preprint reports experimental evidence evaluating an impact on protein function, finding that the variant results in <10% of normal chloride channel conductance relative to wild type (e.g., Bihler_2023, bioRxiv, no PMID). The following publications have been ascertained in the context of this evaluation (PMID: 32084388, 23276700, 26671754, 35527187). Three submitters have reported clinical-significance assessments for this variant to ClinVar after 2014; two submitters classified the variant as pathogenic and one submitter classified it as uncertain significance. Based on the evidence outlined above, the variant was classified as likely pathogenic. |