ClinVar Miner

Submissions for variant NM_004360.5(CDH1):c.1359C>T (p.His453=)

gnomAD frequency: 0.00009  dbSNP: rs114861467
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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000163554 SCV000214112 likely benign Hereditary cancer-predisposing syndrome 2014-08-26 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Invitae RCV000231693 SCV000288429 benign Hereditary diffuse gastric adenocarcinoma 2021-12-12 criteria provided, single submitter clinical testing
Counsyl RCV000231693 SCV000489670 likely benign Hereditary diffuse gastric adenocarcinoma 2016-11-02 criteria provided, single submitter clinical testing
GeneDx RCV000441416 SCV000512519 benign not specified 2015-08-13 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Color Diagnostics, LLC DBA Color Health RCV000163554 SCV000684356 likely benign Hereditary cancer-predisposing syndrome 2015-08-04 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000679560 SCV000806636 likely benign not provided 2017-09-15 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000679560 SCV000888020 benign not provided 2018-02-06 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000441416 SCV000919116 benign not specified 2018-10-22 criteria provided, single submitter clinical testing Variant summary: CDH1 c.1359C>T alters a non-conserved nucleotide resulting in a synonymous change. 4/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00025 in 277242 control chromosomes. The observed variant frequency is approximately 9-fold above the estimated maximal expected allele frequency for a pathogenic variant in CDH1 causing Hereditary Diffuse Gastric Cancer phenotype (2.8e-05), strongly suggesting that the variant is benign. c.1359C>T has been reported in the literature as a somatic mutation in a colorectal tumor, and thus does not provide unequivocal conclusions about association of the variant with Hereditary Diffuse Gastric Cancer . To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
Illumina Laboratory Services,Illumina RCV000231693 SCV001276021 benign Hereditary diffuse gastric adenocarcinoma 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Genetic Services Laboratory,University of Chicago RCV000441416 SCV002066644 likely benign not specified 2021-01-25 criteria provided, single submitter clinical testing
Sema4,Sema4 RCV000163554 SCV002529059 benign Hereditary cancer-predisposing syndrome 2021-09-09 criteria provided, single submitter curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV000441416 SCV002551774 likely benign not specified 2021-11-19 no assertion criteria provided clinical testing

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