Submissions for variant NM_000251.3(MSH2):c.2266A>G (p.Thr756Ala)

dbSNP: rs750646335

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000565456	SCV000662225	uncertain significance	Hereditary cancer-predisposing syndrome	2024-11-22	criteria provided, single submitter	clinical testing	The p.T756A variant (also known as c.2266A>G), located in coding exon 14 of the MSH2 gene, results from an A to G substitution at nucleotide position 2266. The threonine at codon 756 is replaced by alanine, an amino acid with similar properties. In a massively parallel cell-based functional assay testing susceptibility to a DNA damaging agent, 6-thioguanine (6-TG), this variant was determined to be functionally neutral (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. Based on the available evidence, the clinical significance of this variant remains unclear.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000759112	SCV000888218	uncertain significance	not provided	2018-05-17	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000793685	SCV000933050	likely benign	Hereditary nonpolyposis colorectal neoplasms	2025-01-11	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV004000849	SCV004842700	uncertain significance	Lynch syndrome	2024-01-11	criteria provided, single submitter	clinical testing