Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| CFTR2 | RCV000785634 | SCV000924224 | pathogenic | Cystic fibrosis | 2018-08-31 | reviewed by expert panel | research | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000785634 | SCV000917221 | pathogenic | Cystic fibrosis | 2024-05-23 | criteria provided, single submitter | clinical testing | Variant summary: CFTR c.3475T>C (p.Ser1159Pro) results in a non-conservative amino acid change in 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 250707 control chromosomes (gnomAD). c.3475T>C has been reported in the literature in multiple individuals affected with Cystic Fibrosis (e.g. Macek_1993, Simakova_2016, Salinas_2016, McCague_2019). These data indicate that the variant is very likely to be associated with disease. ClinVar contains an entry for this variant (Variation ID: 53756). Based on the evidence outlined above, the variant was classified as pathogenic. |
| Ambry Genetics | RCV000785634 | SCV002614575 | pathogenic | Cystic fibrosis | 2021-03-11 | criteria provided, single submitter | clinical testing | The p.S1159P pathogenic mutation (also known as c.3475T>C), located in coding exon 22 of the CFTR gene, results from a T to C substitution at nucleotide position 3475. The serine at codon 1159 is replaced by proline, an amino acid with similar properties. This alteration has been reported in multiple individuals with cystic fibrosis and a second disease-causing allele (Sosnay PR et al. Nat Genet, 2013 Oct;45:1160-7; Ivanov M et al. BMC Med Genomics, 2018 02;11:13). Based on data from gnomAD, the C allele has an overall frequency of <0.01% (1/250536) total alleles studied. 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 supporting evidence, this alteration is interpreted as a disease-causing mutation. |
| Baylor Genetics | RCV003474581 | SCV004213513 | likely pathogenic | Bronchiectasis with or without elevated sweat chloride 1 | 2023-05-04 | criteria provided, single submitter | clinical testing |