Submissions for variant NM_004360.5(CDH1):c.1015C>G (p.Pro339Ala)

dbSNP: rs1555515709

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000573380	SCV000673180	uncertain significance	Hereditary cancer-predisposing syndrome	2023-12-27	criteria provided, single submitter	clinical testing	The p.P339A variant (also known as c.1015C>G), located in coding exon 8 of the CDH1 gene, results from a C to G substitution at nucleotide position 1015. The proline at codon 339 is replaced by alanine, 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 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	RCV000639228	SCV000760798	uncertain significance	Hereditary diffuse gastric adenocarcinoma	2023-12-12	criteria provided, single submitter	clinical testing	This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 339 of the CDH1 protein (p.Pro339Ala). 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: 485478). 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.
Color Diagnostics, LLC DBA Color Health	RCV000573380	SCV000903636	uncertain significance	Hereditary cancer-predisposing syndrome	2023-12-05	criteria provided, single submitter	clinical testing	This missense variant replaces proline with alanine at codon 339 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 hereditary cancer 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.
GeneDx	RCV001821686	SCV002064153	uncertain significance	not provided	2022-01-19	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on 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)
Baylor Genetics	RCV004569261	SCV005060141	uncertain significance	Familial cancer of breast	2023-11-18	criteria provided, single submitter	clinical testing
GenomeConnect - Invitae Patient Insights Network	RCV003483676	SCV004228928	not provided	Familial cancer of breast; Blepharocheilodontic syndrome 1; Endometrial carcinoma; Hereditary diffuse gastric adenocarcinoma; Ovarian neoplasm; Malignant tumor of prostate		no assertion provided	phenotyping only	Variant interpreted as Uncertain significance and reported on 02-16-2018 by Lab Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.