ClinVar Miner

Submissions for variant NM_004360.5(CDH1):c.1849G>T (p.Ala617Ser)

dbSNP: rs33935154
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000532668 SCV000637753 uncertain significance Hereditary diffuse gastric adenocarcinoma 2023-08-14 criteria provided, single submitter clinical testing An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 617 of the CDH1 protein (p.Ala617Ser). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with CDH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 463732). 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.
Ambry Genetics RCV000561868 SCV000669019 uncertain significance Hereditary cancer-predisposing syndrome 2023-02-02 criteria provided, single submitter clinical testing The p.A617S variant (also known as c.1849G>T), located in coding exon 12 of the CDH1 gene, results from a G to T substitution at nucleotide position 1849. The alanine at codon 617 is replaced by serine, an amino acid with 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.
Color Diagnostics, LLC DBA Color Health RCV000561868 SCV000906594 uncertain significance Hereditary cancer-predisposing syndrome 2019-03-30 criteria provided, single submitter clinical testing
GeneDx RCV001848935 SCV002104331 uncertain significance not provided 2023-07-07 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 15235021, 22850631)
Sema4, Sema4 RCV000561868 SCV002529094 uncertain significance Hereditary cancer-predisposing syndrome 2022-02-15 criteria provided, single submitter curation

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.