Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000490997 | SCV000580611 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2023-04-17 | criteria provided, single submitter | clinical testing | The p.H801P variant (also known as c.2402A>C), located in coding exon 14 of the MSH2 gene, results from an A to C substitution at nucleotide position 2402. The histidine at codon 801 is replaced by proline, an amino acid with similar properties. This variant has been identified in a proband whose Lynch syndrome-associated tumor demonstrated loss of MSH2 and equivocal MSH6 expression by immunohistochemistry (Ambry internal data). 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 Jan;108:163-175). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
| Myriad Genetics, |
RCV003449375 | SCV004186728 | likely pathogenic | Lynch syndrome 1 | 2023-08-08 | criteria provided, single submitter | clinical testing | This variant is considered likely pathogenic. This variant is expected to disrupt protein structure [Myriad internal data]. Functional studies indicate this variant impacts protein function [PMID: 33357406]. |