Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000569362 | SCV000669023 | uncertain significance | Hereditary cancer-predisposing syndrome | 2016-05-06 | criteria provided, single submitter | clinical testing | The p.K664R variant (also known as c.1991A>G), located in coding exon 13 of the CDH1 gene, results from an A to G substitution at nucleotide position 1991. The lysine at codon 664 is replaced by arginine, an amino acid with highly similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6498 samples (12996 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.001% (greater than 175000 alleles tested) in our clinical cohort. 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 |
RCV001858275 | SCV002208836 | uncertain significance | Hereditary diffuse gastric adenocarcinoma | 2023-07-03 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 664 of the CDH1 protein (p.Lys664Arg). 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 tolerated. ClinVar contains an entry for this variant (Variation ID: 483230). 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 0.003%). |
| Baylor Genetics | RCV004569204 | SCV005060130 | uncertain significance | Familial cancer of breast | 2023-11-28 | criteria provided, single submitter | clinical testing |