ClinVar Miner

Submissions for variant NM_004360.5(CDH1):c.578C>T (p.Thr193Ile)

dbSNP: rs970086859
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001184066 SCV001349938 uncertain significance Hereditary cancer-predisposing syndrome 2019-10-02 criteria provided, single submitter clinical testing This missense variant replaces threonine with isoleucine at codon 193 of the CDH1 protein. Computational prediction tool suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold ≤0.5, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV002298886 SCV002597767 uncertain significance Hereditary diffuse gastric adenocarcinoma 2022-09-10 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C15"). ClinVar contains an entry for this variant (Variation ID: 923390). This variant has not been reported in the literature in individuals affected with CDH1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 193 of the CDH1 protein (p.Thr193Ile).
Ambry Genetics RCV001184066 SCV002648940 uncertain significance Hereditary cancer-predisposing syndrome 2021-12-30 criteria provided, single submitter clinical testing The p.T193I variant (also known as c.578C>T), located in coding exon 5 of the CDH1 gene, results from a C to T substitution at nucleotide position 578. The threonine at codon 193 is replaced by isoleucine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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