Total submissions: 9
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ce |
RCV003478392 | SCV004699819 | uncertain significance | not provided | 2023-12-01 | criteria provided, single submitter | clinical testing | CFTR: PM2, PM5:Supporting |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV003478392 | SCV004221695 | uncertain significance | not provided | 2023-06-23 | criteria provided, single submitter | clinical testing | The CFTR c.3877G>A (p.Val1293Ile) variant has been reported in the published literature in an individual with cystic fibrosis (PMID: 28040058 (2016)) and in healthy unaffected individuals (PMID: 16251901 (2006), 11379874 (2001)). The frequency of this variant in the general population, 0.000036 (4/111742 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded conflicting predictions that this variant is deleterious or benign. Based on the available information, we are unable to determine the clinical significance of this variant. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003403550 | SCV004122651 | uncertain significance | not specified | 2025-10-27 | criteria provided, single submitter | clinical testing | Variant summary: CFTR c.3877G>A (p.Val1293Ile) results in a conservative amino acid change located in the ABC transporter-like, ATP-binding domain (IPR003439) of the encoded protein sequence. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change. The variant allele was found at a frequency of 2.8e-05 in 250000 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.3877G>A has been reported in the literature in at least one individual affected with Cystic Fibrosis (e.g., El-Seedy_2016), however without strong evidence for causality. This report therefore does not provide unequivocal conclusions about association of the variant with Cystic Fibrosis. At least one publication reports experimental evidence evaluating an impact on protein function (e.g., Bihler_2023, no PMID). These results showed no damaging effect of this variant. The following publications have been ascertained in the context of this evaluation (PMID: 28040058, 11379874, 20974851, 15536480, 16251901, 17244607). ClinVar contains an entry for this variant (Variation ID: 552594). Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Fulgent Genetics, |
RCV002477491 | SCV002780958 | uncertain significance | Bronchiectasis with or without elevated sweat chloride 1; Cystic fibrosis; Hereditary pancreatitis; Congenital bilateral aplasia of vas deferens from CFTR mutation | 2021-07-08 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV000667886 | SCV002624882 | uncertain significance | Cystic fibrosis | 2024-07-08 | criteria provided, single submitter | clinical testing | The p.V1293I variant (also known as c.3877G>A), located in coding exon 24 of the CFTR gene, results from a G to A substitution at nucleotide position 3877. The valine at codon 1293 is replaced by isoleucine, an amino acid with highly similar properties. This variant was identified in a cystic fibrosis cohort with no second CFTR varaint and in a control sample (El-Seedy A et al. Cell. Mol. Biol. (Noisy-le-grand), 2016 Nov;62:21-28; Le Maréchal C et al. Hum. Genet., 2001 Apr;108:290-8). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |
| Genome- |
RCV000667886 | SCV002027522 | uncertain significance | Cystic fibrosis | 2021-09-05 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000667886 | SCV001421825 | uncertain significance | Cystic fibrosis | 2025-04-03 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 1293 of the CFTR protein (p.Val1293Ile). This variant is present in population databases (rs769931559, gnomAD 0.004%). This missense change has been observed in individual(s) with cystic fibrosis (PMID: 12815607, 28040058). ClinVar contains an entry for this variant (Variation ID: 552594). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt CFTR protein function with a negative predictive value of 80%. 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. |
| Natera, |
RCV001835084 | SCV002075901 | uncertain significance | CFTR-related disorder | 2018-05-24 | no assertion criteria provided | clinical testing | |
| Counsyl | RCV000667886 | SCV000792398 | uncertain significance | Cystic fibrosis | 2017-06-27 | no assertion criteria provided | clinical testing | This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact variantquestions@myriad.com. |