Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001058351 | SCV001222911 | uncertain significance | Cystic fibrosis | 2021-09-02 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine with leucine at codon 1413 of the CFTR protein (p.Phe1413Leu). The phenylalanine residue is moderately conserved and there is a small physicochemical difference between phenylalanine and leucine. This variant is present in population databases (rs142092183, ExAC 0.002%). This variant has not been reported in the literature in individuals affected with CFTR-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001201223 | SCV001372315 | uncertain significance | not specified | 2020-06-18 | criteria provided, single submitter | clinical testing | Variant summary: CFTR c.4237T>C (p.Phe1413Leu) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 250714 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.4237T>C in individuals affected with Chronic Pancreatitis Risk and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
Genome- |
RCV001058351 | SCV002027545 | uncertain significance | Cystic fibrosis | 2021-09-05 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV001058351 | SCV002630464 | uncertain significance | Cystic fibrosis | 2021-12-27 | criteria provided, single submitter | clinical testing | The p.F1413L variant (also known as c.4237T>C), located in coding exon 26 of the CFTR gene, results from a T to C substitution at nucleotide position 4237. The phenylalanine at codon 1413 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Natera, |
RCV001827365 | SCV002075953 | uncertain significance | CFTR-related disorders | 2018-06-28 | no assertion criteria provided | clinical testing |