ClinVar Miner

Submissions for variant NM_004360.5(CDH1):c.1096A>G (p.Thr366Ala)

dbSNP: rs1060501238
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000456768 SCV000545442 uncertain significance Hereditary diffuse gastric adenocarcinoma 2022-02-17 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 366 of the CDH1 protein (p.Thr366Ala). This variant is present in population databases (no rsID available, gnomAD 0.006%). 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: 406653). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest 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 RCV000583142 SCV000689432 uncertain significance Hereditary cancer-predisposing syndrome 2023-12-05 criteria provided, single submitter clinical testing This missense variant replaces threonine with alanine at codon 366 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 1/251476 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.
Ambry Genetics RCV000583142 SCV002738492 uncertain significance Hereditary cancer-predisposing syndrome 2021-07-27 criteria provided, single submitter clinical testing The p.T366A variant (also known as c.1096A>G), located in coding exon 8 of the CDH1 gene, results from an A to G substitution at nucleotide position 1096. The threonine at codon 366 is replaced by alanine, an amino acid with similar properties. This amino acid position is not well 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.
Baylor Genetics RCV003463876 SCV004215704 uncertain significance Familial cancer of breast 2023-06-29 criteria provided, single submitter clinical testing

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