Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000572516 | SCV000665277 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-09-14 | criteria provided, single submitter | clinical testing | The p.D881N variant (also known as c.2641G>A), located in coding exon 16 of the CDH1 gene, results from a G to A substitution at nucleotide position 2641. The aspartic acid at codon 881 is replaced by asparagine, 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. |
| Labcorp Genetics |
RCV000796701 | SCV000936225 | uncertain significance | Hereditary diffuse gastric adenocarcinoma | 2023-03-26 | 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. 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 disruptive. ClinVar contains an entry for this variant (Variation ID: 481114). This variant has not been reported in the literature in individuals affected with CDH1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 881 of the CDH1 protein (p.Asp881Asn). |
| Prevention |
RCV003403352 | SCV004110715 | uncertain significance | CDH1-related disorder | 2023-09-04 | criteria provided, single submitter | clinical testing | The CDH1 c.2641G>A variant is predicted to result in the amino acid substitution p.Asp881Asn. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.00088% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/16-68867394-G-A) and is interpreted as uncertain significance in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/481114/). A different nucleotide substitution affecting the same amino acid (p.Asp881Glu) has been reported in an individual with triple-negative breast cancer (Table S2, Liu et al. 2017. PubMed ID: 28135048). At this time, the clinical significance of the c.2641G>A (p.Asp881Asn) variant is uncertain due to the absence of conclusive functional and genetic evidence. |
| Color Diagnostics, |
RCV000572516 | SCV004361289 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-12-04 | criteria provided, single submitter | clinical testing | This missense variant replaces aspartic acid with asparagine at codon 881 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 been identified in 1/251390 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. |