Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV003311326 | SCV004007972 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-05-13 | criteria provided, single submitter | clinical testing | The c.2355_2356ins13 variant, located in coding exon 15 of the CDH1 gene, results from an insertion of 13 nucleotides (CAACCCTCATGGT) at nucleotide positions 2355 to 2356, causing a translational frameshift with a predicted alternate stop codon (p.D786Qfs*5). This alteration has been observed in at least one individual with a personal and/or family history that is consistent with CDH1-related disease (Ambry internal data). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
| Myriad Genetics, |
RCV003336847 | SCV004043081 | pathogenic | Hereditary diffuse gastric adenocarcinoma | 2023-06-15 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |
| Color Diagnostics, |
RCV003311326 | SCV004360527 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-08-21 | criteria provided, single submitter | clinical testing | This variant inserts 13 nucleotides in exon 15 of the CDH1 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in an individual and/or family affected with CDH1-related disease (ClinVar SCV004007972.1). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of CDH1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. |
| Labcorp Genetics |
RCV003336847 | SCV004397248 | pathogenic | Hereditary diffuse gastric adenocarcinoma | 2023-10-08 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Asp786Glnfs*5) in the CDH1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CDH1 are known to be pathogenic (PMID: 15235021, 20373070). 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: 2567612). For these reasons, this variant has been classified as Pathogenic. |