Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002444168 | SCV002754160 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-02-03 | criteria provided, single submitter | clinical testing | The p.N376T variant (also known as c.1127A>C), located in coding exon 8 of the CDH1 gene, results from an A to C substitution at nucleotide position 1127. The asparagine at codon 376 is replaced by threonine, an amino acid with similar properties. This amino acid position is not 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 |
RCV003103009 | SCV003199646 | uncertain significance | Hereditary diffuse gastric adenocarcinoma | 2022-05-27 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with CDH1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with threonine, which is neutral and polar, at codon 376 of the CDH1 protein (p.Asn376Thr). 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. |