Total submissions: 6
| 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 | |
| Labcorp Genetics |
RCV000007637 | SCV001505750 | uncertain significance | Cystic fibrosis | 2020-07-30 | criteria provided, single submitter | clinical testing | 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). 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. 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. This variant is not present in population databases (ExAC no frequency). 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. |
| 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 |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000007637 | SCV005076478 | pathogenic | Cystic fibrosis | 2024-04-25 | criteria provided, single submitter | clinical testing | Variant summary: CFTR c.3746G>A (p.Gly1249Glu) results in a non-conservative amino acid change located in the ABC transporter-like, 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 was absent in 251006 control chromosomes. c.3746G>A has been reported in the literature in at-least four individuals affected with Cystic Fibrosis (Banjar_2020, Dork_1998, Geurts_2020, Greil_1993). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Additionally, at least one variant at the Gly1249 residue has been reported as associated with disease (c.3745G>A, p.Gly1249Arg), suggesting that this codon is functionally important. These data indicate that the variant is very likely to be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 32292813, 9683582, 32084388, 7520022). ClinVar contains an entry for this variant (Variation ID: 7216). Based on the evidence outlined above, the variant was classified as pathogenic. |
| OMIM | RCV000007637 | SCV000027838 | pathogenic | Cystic fibrosis | 1994-07-01 | no assertion criteria provided | literature only |