Submissions for variant NM_004360.5(CDH1):c.1438G>A (p.Val480Met)

dbSNP: rs786202675

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000165603	SCV000216337	uncertain significance	Hereditary cancer-predisposing syndrome	2021-11-16	criteria provided, single submitter	clinical testing	The p.V480M variant (also known as c.1438G>A), located in coding exon 10 of the CDH1 gene, results from a G to A substitution at nucleotide position 1438. The valine at codon 480 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000801471	SCV000941248	uncertain significance	Hereditary diffuse gastric adenocarcinoma	2023-11-20	criteria provided, single submitter	clinical testing	This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 480 of the CDH1 protein (p.Val480Met). This variant is not present in population databases (gnomAD no frequency). 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: 186076). 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. 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.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000985651	SCV001134054	uncertain significance	not provided	2018-10-15	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000165603	SCV004360483	uncertain significance	Hereditary cancer-predisposing syndrome	2023-12-05	criteria provided, single submitter	clinical testing	This missense variant replaces valine with methionine at codon 480 of the CDH1 protein. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with CDH1-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Baylor Genetics	RCV004567277	SCV005060098	uncertain significance	Familial cancer of breast	2024-01-19	criteria provided, single submitter	clinical testing
GeneDx	RCV000985651	SCV005378284	uncertain significance	not provided	2023-11-19	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)