Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Mayo Clinic Laboratories, |
RCV003481052 | SCV004224075 | uncertain significance | not provided | 2023-03-21 | criteria provided, single submitter | clinical testing | PP3, PM2 |
| Genomic Medicine Center of Excellence, |
RCV001283850 | SCV004808221 | uncertain significance | Cystic fibrosis | 2024-03-29 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004800960 | SCV005422416 | uncertain significance | not specified | 2024-10-11 | criteria provided, single submitter | clinical testing | Variant summary: CFTR c.1993A>T (p.Thr665Ser) results in a conservative amino acid change located in the CFTR regulator domain (IPR025837) and Cystic fibrosis transmembrane conductance regulator, ATP-binding cassette domain 1 (IPR047082) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant strengthened a cryptic 3' acceptor in exon 14 in an in vitro minigene assay (Aznarez_2003). However the abnormal splicing products were also observed in WT and other nearby variants, and consensus agreement among computation tools predict no significant impact on normal splicing. The variant was absent in 250140 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1993A>T has been reported in the literature in at-least two individuals affected with Cystic Fibrosis, however in one case, the second variant in CFTR was not identified (Naguib_2006), and in the other case, the full information was not available for analysis (Messaoud_1996). These report(s) do not provide unequivocal conclusions about association of the variant with Cystic Fibrosis. At least one publication reports experimental evidence evaluating an impact on splicing effects, however, does not allow convincing conclusions about the variant effect (Aznarez_2003). The following publications have been ascertained in the context of this evaluation (PMID: 12913074, 8800923, 16837250). ClinVar contains an entry for this variant (Variation ID: 993031). Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Fulgent Genetics, |
RCV005040129 | SCV005673348 | likely pathogenic | Bronchiectasis with or without elevated sweat chloride 1; Cystic fibrosis; Hereditary pancreatitis; Congenital bilateral aplasia of vas deferens from CFTR mutation | 2024-03-18 | criteria provided, single submitter | clinical testing | |
| Biochemical Molecular Genetic Laboratory, |
RCV001283850 | SCV001469286 | likely pathogenic | Cystic fibrosis | 2020-10-11 | no assertion criteria provided | clinical testing |