Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000561280 | SCV000669039 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-09-13 | criteria provided, single submitter | clinical testing | The c.1163_1171dupAGGCTAACG variant (also known as p.E388_N390dup), located in coding exon 9 of the CDH1 gene, results from an in-frame duplication of AGGCTAACG at nucleotide positions 1163 to 1171. This results in the duplication of 3 extra residues (EAN) at codons 388 to 390. This amino acid region is not well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Color Diagnostics, |
RCV000561280 | SCV000908732 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-05-06 | criteria provided, single submitter | clinical testing | This variant causes a duplication of 3 amino acids in 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 1/251480 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. |
Labcorp Genetics |
RCV000804593 | SCV000944510 | uncertain significance | Hereditary diffuse gastric adenocarcinoma | 2023-07-16 | 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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 483242). This variant has not been reported in the literature in individuals affected with CDH1-related conditions. This variant is present in population databases (rs772580163, gnomAD 0.002%). This variant, c.1163_1171dup, results in the insertion of 3 amino acid(s) of the CDH1 protein (p.Glu388_Asn390dup), but otherwise preserves the integrity of the reading frame. |
Prevention |
RCV003420011 | SCV004106199 | uncertain significance | CDH1-related disorder | 2023-09-15 | criteria provided, single submitter | clinical testing | The CDH1 c.1163_1171dup9 variant is predicted to result in an in-frame duplication (p.Glu388_Asn390dup). 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/16-68847236-G-GAACGAGGCT). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |