Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000199237 | SCV000254831 | uncertain significance | Hereditary diffuse gastric adenocarcinoma | 2024-01-14 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 21 of the CDH1 protein (p.Leu21Phe). This variant is not present in population databases (gnomAD no frequency). 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: 216596). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests 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, |
RCV001525987 | SCV001736222 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-11-16 | criteria provided, single submitter | clinical testing | This missense variant replaces leucine with phenylalanine at codon 21 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 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. |
Ambry Genetics | RCV001525987 | SCV002655331 | uncertain significance | Hereditary cancer-predisposing syndrome | 2017-12-14 | criteria provided, single submitter | clinical testing | The p.L21F variant (also known as c.61C>T), located in coding exon 2 of the CDH1 gene, results from a C to T substitution at nucleotide position 61. The leucine at codon 21 is replaced by phenylalanine, an amino acid with highly similar properties. 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. |
Baylor Genetics | RCV003462333 | SCV004215660 | uncertain significance | Familial cancer of breast | 2023-08-22 | criteria provided, single submitter | clinical testing |