Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
CFTR2 | RCV000576486 | SCV000677602 | pathogenic | Cystic fibrosis | 2017-03-17 | reviewed by expert panel | research | |
Eurofins Ntd Llc |
RCV000726994 | SCV000704794 | likely pathogenic | not provided | 2016-12-27 | criteria provided, single submitter | clinical testing | |
Mendelics | RCV000576486 | SCV000886225 | pathogenic | Cystic fibrosis | 2018-11-05 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000576486 | SCV001362680 | pathogenic | Cystic fibrosis | 2022-01-27 | criteria provided, single submitter | clinical testing | Variant summary: CFTR c.3468+2dupT (also called as 3600+2insT or c.3468+2_3468+3insT, according to an older nomenclature) alters a nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Several computational tools predict a significant impact on normal splicing: four predict the variant abolishes a 5' splicing donor site. At least one publication reported experimental evidence confirming in a mini-gene assay that this variant affects mRNA splicing, and demonstrated no detectable protein in transfected HEK293 cells (Joynt_2020). The variant was absent in 250770 control chromosomes (gnomAD). c.3468+2dupT has been reported in the literature in multiple individuals affected with Cystic Fibrosis (e.g. Van Biervliet 2007, Krenkova 2012, Zietkiewicz 2014, Medza_2021). These data indicate that the variant is very likely to be associated with disease. Four clinical diagnostic laboratories (including an expert panel, CFTR2) have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and all laboratories classified the variant as pathogenic/likely pathogenic, and the expert panel has classified the variant pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
Institute of Human Genetics, |
RCV000576486 | SCV002574079 | pathogenic | Cystic fibrosis | 2022-09-05 | criteria provided, single submitter | curation | This variant was identified in 7 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: PVS1, PS3_SUP, PM2_SUP, PM3_VSTR, PP4 |
Baylor Genetics | RCV003465284 | SCV004215760 | likely pathogenic | Bronchiectasis with or without elevated sweat chloride 1 | 2022-11-17 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV000576486 | SCV001461262 | pathogenic | Cystic fibrosis | 2020-09-16 | no assertion criteria provided | clinical testing |