Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000214994 | SCV000277809 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-03-25 | criteria provided, single submitter | clinical testing | The p.P30R variant (also known as c.89C>G), located in coding exon 2 of the CDH1 gene, results from a C to G substitution at nucleotide position 89. The proline at codon 30 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Color Diagnostics, |
RCV000214994 | SCV001351093 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-11-05 | criteria provided, single submitter | clinical testing | This missense variant replaces proline with arginine at codon 30 of the CDH1 protein. Computational prediction tool is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/156486 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 |
RCV001219839 | SCV001391797 | uncertain significance | Hereditary diffuse gastric adenocarcinoma | 2024-01-08 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 30 of the CDH1 protein (p.Pro30Arg). This variant is present in population databases (no rsID available, 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: 233438). 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. 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. |
European Reference Network on Genetic Tumour Risk Syndromes |
RCV001219839 | SCV003926981 | uncertain significance | Hereditary diffuse gastric adenocarcinoma | 2022-08-01 | criteria provided, single submitter | clinical testing | PM2 (PMID: 30311375) |