Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Baylor Genetics | RCV001004469 | SCV001163514 | likely pathogenic | Cystic fibrosis; Congenital bilateral aplasia of vas deferens from CFTR mutation | criteria provided, single submitter | clinical testing | ||
| Ambry Genetics | RCV002415501 | SCV002728448 | uncertain significance | Cystic fibrosis | 2021-08-20 | criteria provided, single submitter | clinical testing | The p.R709Q variant (also known as c.2126G>A), located in coding exon 14 of the CFTR gene, results from a G to A substitution at nucleotide position 2126. The arginine at codon 709 is replaced by glutamine, an amino acid with highly similar properties. In a study of Czech cystic fibrosis patients, this alteration was found to be in cis with p.E292K in four unrelated families. In one patient, the E292K-R709Q complex allele was descried to be in trans with a pathogenic mutation in CFTR (Kenková P et al. J. Cyst. Fibros., 2013 Sep;12:532-7). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003155057 | SCV003844308 | uncertain significance | not specified | 2024-06-25 | criteria provided, single submitter | clinical testing | Variant summary: CFTR c.2126G>A (p.Arg709Gln) results in a conservative amino acid change located in the CFTR regulator domain (IPR025837) of the encoded protein sequence. Three of four in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 250858 control chromosomes (gnomAD). c.2126G>A has been reported in the literature as a complex allele, in cis with c.874G>A (p.Glu292Lys), in individuals affected with Cystic Fibrosis (Krenkova_2013), where the genotype for one affected was provided, who had a pathogenic variant trans in CFTR. This report does not provide unequivocal conclusions about association of the variant with Cystic Fibrosis. At least one publication reports experimental evidence evaluating the variant's impact on protein function in isolation, demonstrating that the variant resulted in approximately 10% of normal chloride channel conductance relative to wild type (e.g. Bihler_2024). ClinVar contains an entry for this variant (Variation ID: 53441). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. |
| Baylor Genetics | RCV004566870 | SCV005057411 | likely pathogenic | Bronchiectasis with or without elevated sweat chloride 1 | 2024-03-25 | criteria provided, single submitter | clinical testing |