Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001003496 | SCV000696840 | likely pathogenic | Cystic fibrosis | 2023-05-01 | criteria provided, single submitter | clinical testing | Variant summary: CFTR c.1394C>A (p.Thr465Asn) results in a non-conservative amino acid change located in the ABC transporter-like domain and ATPase 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 allele was found at a frequency of 4e-06 in 251196 control chromosomes. c.1394C>A has been reported in the literature in individuals affected with Cystic Fibrosis (example, Kammesheidt_2006, Lucarelli_2015, Bozdogan_2021, Raraigh_2022) as well as at least one CBAVD patient (example, Yuan_2019). One internal sample and their affected sibling also tested positive for this variant with deltaF508 in trans. These data indicate that the variant likely associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 16980811, 25910067, 22504961, 33572515, 35913788, 34782259, 30811104). Three ClinVar submitters (evaluation after 2014) have cited the variant with conflicting assessments: two submitters classified the variant as uncertain significance, and one submitter classified it as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Clinical Molecular Genetics Laboratory, |
RCV001003496 | SCV000994913 | likely pathogenic | Cystic fibrosis | 2019-09-30 | criteria provided, single submitter | clinical testing | Identified in combination with F508del in two affected siblings |
| Baylor Genetics | RCV001004450 | SCV001163495 | likely pathogenic | Cystic fibrosis; Congenital bilateral aplasia of vas deferens from CFTR mutation | criteria provided, single submitter | clinical testing | ||
| Mayo Clinic Laboratories, |
RCV000586527 | SCV001714235 | uncertain significance | not provided | 2019-11-25 | criteria provided, single submitter | clinical testing | |
| Genome- |
RCV001003496 | SCV001822051 | uncertain significance | Cystic fibrosis | 2021-07-22 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV003471939 | SCV004213362 | likely pathogenic | Bronchiectasis with or without elevated sweat chloride 1 | 2023-12-01 | criteria provided, single submitter | clinical testing |