ClinVar Miner

Submissions for variant NM_004360.5(CDH1):c.808T>G (p.Ser270Ala) (rs587776399)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000130793 SCV000185687 likely benign Hereditary cancer-predisposing syndrome 2017-06-30 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (benign),Other data supporting benign classification
GeneDx RCV000235151 SCV000210905 uncertain significance not provided 2018-06-12 criteria provided, single submitter clinical testing This variant is denoted CDH1 c.808T>G at the cDNA level, p.Ser270Ala (S270A) at the protein level, and results in the change of a Serine to an Alanine (TCT>GCT). This variant has been observed in a family with a history of prostate and gastric cancer and three additional prostate cancer kindreds, with the variant segregating with prostate cancer diagnoses in most families (Ikonen 2001). Additionally, CDH1 Ser270Ala was found to be more prevalent in individuals with familial and non-familial prostate cancer (10/582) as compared to controls (5/923) (Ikonen 2001). Functional work shows this variant to behave similar to wildtype in a cell migration assay but to show strong adhesion, albeit less than WT, in an adhesion assay (Petrova 2016). CDH1 Ser270Ala was observed at an allele frequency of 0.23% (60/25,794) in individuals of Finnish ancestry in large population cohorts (Lek 2016). This variant is located in the cadherin 2 domain of the extracellular domain (Brooks-Wilson 2004, Figueiredo 2013). In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether CDH1 Ser270Ala is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000144457 SCV000254832 likely benign Hereditary diffuse gastric cancer 2017-12-18 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000144457 SCV000398554 likely benign Hereditary diffuse gastric cancer 2016-06-14 criteria provided, single submitter clinical testing
Counsyl RCV000144457 SCV000786564 likely benign Hereditary diffuse gastric cancer 2018-05-23 criteria provided, single submitter clinical testing
Color RCV000130793 SCV000910717 likely benign Hereditary cancer-predisposing syndrome 2016-03-17 criteria provided, single submitter clinical testing
Laboratório de Genética Humana e Médica, Universidade Federal do Pará RCV000144457 SCV000189523 untested Hereditary diffuse gastric cancer no assertion provided not provided Converted during submission to not provided.

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