ClinVar Miner

Submissions for variant NM_004360.5(CDH1):c.417G>C (p.Leu139Phe)

dbSNP: rs1057521858
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000706184 SCV000835221 uncertain significance Hereditary diffuse gastric adenocarcinoma 2018-02-15 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with CDH1-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with phenylalanine at codon 139 of the CDH1 protein (p.Leu139Phe). The leucine residue is weakly conserved and there is a small physicochemical difference between leucine and phenylalanine.
Mendelics RCV000706184 SCV000839078 uncertain significance Hereditary diffuse gastric adenocarcinoma 2018-07-02 criteria provided, single submitter clinical testing
Ambry Genetics RCV001021997 SCV001183684 uncertain significance Hereditary cancer-predisposing syndrome 2022-05-03 criteria provided, single submitter clinical testing The p.L139F variant (also known as c.417G>C), located in coding exon 4 of the CDH1 gene, results from a G to C substitution at nucleotide position 417. The leucine at codon 139 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.