ClinVar Miner

Submissions for variant NM_004360.5(CDH1):c.2227C>T (p.Pro743Ser)

dbSNP: rs786203005
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000166116 SCV000216885 uncertain significance Hereditary cancer-predisposing syndrome 2023-01-18 criteria provided, single submitter clinical testing The p.P743S variant (also known as c.2227C>T), located in coding exon 14 of the CDH1 gene, results from a C to T substitution at nucleotide position 2227. The proline at codon 743 is replaced by serine, an amino acid with similar properties. This alteration was identified in a cohort of 1040 patients with advanced cancer; however, specific clinical information on this individual was not provided (Mandelker D et al. JAMA, 2017 09;318:825-835). This amino acid position is 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.
Color Diagnostics, LLC DBA Color Health RCV000166116 SCV000684410 uncertain significance Hereditary cancer-predisposing syndrome 2019-04-04 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001048843 SCV001212868 uncertain significance Hereditary diffuse gastric adenocarcinoma 2023-01-24 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 186510). 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 proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 743 of the CDH1 protein (p.Pro743Ser).
Baylor Genetics RCV004567294 SCV005060068 uncertain significance Familial cancer of breast 2024-02-29 criteria provided, single submitter clinical testing

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