Submissions for variant NM_004360.5(CDH1):c.1202C>A (p.Ala401Asp)

gnomAD frequency: 0.00001  dbSNP: rs150795245

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000486692	SCV000572282	uncertain significance	not provided	2023-12-05	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)
Ambry Genetics	RCV000566539	SCV000668991	uncertain significance	Hereditary cancer-predisposing syndrome	2023-07-06	criteria provided, single submitter	clinical testing	The p.A401D variant (also known as c.1202C>A), located in coding exon 9 of the CDH1 gene, results from a C to A substitution at nucleotide position 1202. The alanine at codon 401 is replaced by aspartic acid, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species, and aspartic acid is the reference amino acid in other 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000639286	SCV000760857	benign	Hereditary diffuse gastric adenocarcinoma	2024-01-29	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000566539	SCV000908734	uncertain significance	Hereditary cancer-predisposing syndrome	2023-12-05	criteria provided, single submitter	clinical testing	This missense variant replaces alanine with aspartic acid at codon 401 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 been identified in 1/251488 chromosomes 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.
PreventionGenetics, part of Exact Sciences	RCV003419813	SCV004108310	uncertain significance	CDH1-related disorder	2023-06-23	criteria provided, single submitter	clinical testing	The CDH1 c.1202C>A variant is predicted to result in the amino acid substitution p.Ala401Asp. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0062% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/16-68847280-C-A). In ClinVar, this variant is interpreted as benign/uncertain (https://preview.ncbi.nlm.nih.gov/clinvar/variation/422738/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Baylor Genetics	RCV003464032	SCV004215668	uncertain significance	Familial cancer of breast	2023-08-15	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000486692	SCV004220780	uncertain significance	not provided	2015-10-10	criteria provided, single submitter	clinical testing	To the best of our knowledge, this variant has not been reported in the published literature. The frequency of this variant in the general population, 0.000004 (1/251488 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Based on the available information, we are unable to determine the clinical significance of this variant.