Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000046979 | SCV000220176 | likely benign | Cystic fibrosis | 2014-03-18 | criteria provided, single submitter | literature only | |
| Mendelics | RCV000046979 | SCV001137496 | benign | Cystic fibrosis | 2019-05-28 | criteria provided, single submitter | clinical testing | |
| Institute of Human Genetics, |
RCV000046979 | SCV002573933 | uncertain significance | Cystic fibrosis | 2022-09-05 | criteria provided, single submitter | curation | This variant was identified in 1 patient with a clinically confirmed diagnosis of cystic fibrosis. The variant was classified in the context of a project re-classifying variants in the German Cystic Fibrosis Registry (Muko.e.V.). Link: https://www.muko.info/angebote/qualitaetsmanagement/register/cf-einrichtungen/mukoweb. Criteria applied: PM2_SUP, PP3 |
| Ambry Genetics | RCV000046979 | SCV002625984 | likely benign | Cystic fibrosis | 2018-11-14 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| Labcorp Genetics |
RCV000046979 | SCV003454470 | uncertain significance | Cystic fibrosis | 2022-05-25 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1257 of the CFTR protein (p.Phe1257Leu). This variant is present in population databases (rs397508607, gnomAD 0.01%). This missense change has been observed in individual(s) with cystic fibrosis (PMID: 11379874). ClinVar contains an entry for this variant (Variation ID: 53809). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |