ClinVar Miner

Submissions for variant NM_004360.5(CDH1):c.2261A>G (p.Tyr754Cys)

gnomAD frequency: 0.00001  dbSNP: rs767613429
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000165420 SCV000216149 likely benign Hereditary cancer-predisposing syndrome 2021-03-04 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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.
Counsyl RCV000411136 SCV000489304 uncertain significance Hereditary diffuse gastric adenocarcinoma 2016-09-14 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000411136 SCV000545461 likely benign Hereditary diffuse gastric adenocarcinoma 2023-11-06 criteria provided, single submitter clinical testing
GeneDx RCV000485531 SCV000567175 uncertain significance not provided 2022-12-29 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: 22252131, 15235021, 22850631)
Color Diagnostics, LLC DBA Color Health RCV000165420 SCV000684413 uncertain significance Hereditary cancer-predisposing syndrome 2022-06-27 criteria provided, single submitter clinical testing This missense variant replaces tyrosine with cysteine at codon 754 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 been identified in 3/282888 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.
Revvity Omics, Revvity RCV000485531 SCV003831018 uncertain significance not provided 2022-01-26 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV000411136 SCV004019530 uncertain significance Hereditary diffuse gastric adenocarcinoma 2023-03-03 criteria provided, single submitter clinical testing This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000485531 SCV004220817 uncertain significance not provided 2024-12-02 criteria provided, single submitter clinical testing The CDH1 c.2261A>G (p.Tyr754Cys) variant has been reported in the published literature in a cohort of women identified as having low risk for breast cancer (PMID: 38153744 (2023)). The frequency of this variant in the general population, 0.000023 (3/129186 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded conflicting predictions that this variant is benign or damaging. Based on the available information, we are unable to determine the clinical significance of this variant.
Baylor Genetics RCV004567271 SCV005060087 uncertain significance Familial cancer of breast 2024-02-09 criteria provided, single submitter clinical testing

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