ClinVar Miner

Submissions for variant NM_004360.5(CDH1):c.1153C>T (p.Pro385Ser)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002349363 SCV002623040 uncertain significance Hereditary cancer-predisposing syndrome 2022-02-15 criteria provided, single submitter clinical testing The p.P385S variant (also known as c.1153C>T), located in coding exon 9 of the CDH1 gene, results from a C to T substitution at nucleotide position 1153. The proline at codon 385 is replaced by serine, an amino acid with similar properties. This alteration was observed in 1/7,051 unselected female breast cancer patients and was not observed in 11,241 female controls, 53 unselected male breast cancer patients, or 12,490 male controls of Japanese ancestry (Momozawa Y et al. Nat Commun, 2018 10;9:4083). 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV003094351 SCV003473199 uncertain significance Hereditary diffuse gastric adenocarcinoma 2022-03-20 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This missense change has been observed in individual(s) with breast cancer (PMID: 30287823). 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 385 of the CDH1 protein (p.Pro385Ser).

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