Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
International Society for Gastrointestinal Hereditary Tumours |
RCV000076445 | SCV000107473 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Multifactorial likelihood analysis posterior probability >0.99 |
Ambry Genetics | RCV000561670 | SCV000669869 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-11-30 | criteria provided, single submitter | clinical testing | The p.G751R pathogenic mutation (also known as c.2251G>A), located in coding exon 14 of the MSH2 gene, results from a G to A substitution at nucleotide position 2251. The glycine at codon 751 is replaced by arginine, an amino acid with dissimilar properties. This variant has been reported in multiple individuals/families diagnosed with HNPCC (Dieumegard B et al. Br. J. Cancer, 2000 Feb;82:871-80; De Lellis L et al. PLoS One, 2013 Nov;8:e81194; Talbot A et al. BMC Cancer, 2021 May;21:617). Functional analysis of the yeast equivalent alteration (msh2-G770R) have shown intermediate Msh2 expression relative to wild type and deficient DNA repair function (Gammie AE et al. Genetics, 2007 Oct;177:707-21). In a massively parallel cell-based functional assay testing susceptibility to a DNA damaging agent, 6-thioguanine (6-TG), this variant was reported to be functionally deleterious (Jia X et al. Am J Hum Genet, 2021 01;108:163-175). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. |
Myriad Genetics, |
RCV003452902 | SCV004186736 | likely pathogenic | Lynch syndrome 1 | 2023-08-08 | criteria provided, single submitter | clinical testing | This variant is considered likely pathogenic. This variant is strongly associated with more severe personal and family histories of cancer, typical for individuals with pathogenic variants in this gene [PMID: 27363726]. |
Baylor Genetics | RCV003452902 | SCV004196848 | pathogenic | Lynch syndrome 1 | 2023-05-10 | criteria provided, single submitter | clinical testing |