Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000577019 | SCV001361662 | likely pathogenic | Cystic fibrosis | 2023-10-10 | criteria provided, single submitter | clinical testing | Variant summary: CFTR c.709C>G (p.Gln237Glu) results in a conservative amino acid change located in the transmembrane domain (IPR011527) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 251392 control chromosomes (gnomAD). c.709C>G has been reported in the literature and in multiple databases in individuals affected with Cystic Fibrosis, including multiple examples where it was found in the compound heterozygous state together with a pathogenic variant (e.g. Claustres_2000, Hubert_2004, Giardet_2007, Gaitch_2016, DeWachter_2017, Ramalho_2021, Vaidyanathan_2022); however, in two of these cases, the individual either was asymptomatic or had a mild phenotype/late disease onset (e.g. Ramhalo_2021, Mekki_2021), suggesting this variant may have varying clinical consequences. These data indicate that the variant is likely to be associated with disease. At least one publication reports experimental evidence evaluating forskolin induced swelling (FIS) of organoids from a CF patient with the genotype F508del/Q237E, and found there was some residual CFTR function that improved with treatment with ivacaftor, however, as the variant was not examined in isolation, it does not allow convincing conclusions about the variant effect. The following publications have been ascertained in the context of this evaluation (PMID: 10923036, 28830496, 27086061, 17850636, 15463882, 33946859, 32747394, 35857025). One submitter has cited a clinical-significance assessment for this variant to ClinVar after 2014 and has classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| CFTR- |
RCV002281557 | SCV002570011 | pathogenic | Cystic fibrosis; CFTR-related disorder | 2020-09-02 | criteria provided, single submitter | curation | when the variant is in trans with another CF-causing variation, can either result in CF or in a CFTR-RD |
| Baylor Genetics | RCV004566887 | SCV005057422 | likely pathogenic | Bronchiectasis with or without elevated sweat chloride 1 | 2024-03-12 | criteria provided, single submitter | clinical testing | |
| Clin |
RCV000577019 | SCV000679170 | not provided | Cystic fibrosis | no assertion provided | literature only |