Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Mendelics | RCV000007637 | SCV000886364 | uncertain significance | Cystic fibrosis | 2018-11-05 | criteria provided, single submitter | clinical testing | |
CFTR- |
RCV000007637 | SCV001169363 | pathogenic | Cystic fibrosis | 2018-01-29 | criteria provided, single submitter | curation | |
Invitae | RCV000007637 | SCV001505750 | uncertain significance | Cystic fibrosis | 2020-07-30 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with glutamic acid at codon 1249 of the CFTR protein (p.Gly1249Glu). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and glutamic acid. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of cystic fibrosis (PMID: 8880589, 7520022). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 7216). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Institute of Human Genetics, |
RCV000007637 | SCV002573864 | likely pathogenic | Cystic fibrosis | 2022-09-05 | criteria provided, single submitter | curation | This variant was identified in 4 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, PP3, PP4 |
OMIM | RCV000007637 | SCV000027838 | pathogenic | Cystic fibrosis | 1994-07-01 | no assertion criteria provided | literature only |