ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.1748A>G (p.Asn583Ser) (rs201118107)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 12
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000115510 SCV000186283 likely benign Hereditary cancer-predisposing syndrome 2018-05-01 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (benign),Other data supporting benign classification
Biesecker Lab/Human Development Section,National Institutes of Health RCV000034553 SCV000043343 variant of unknown significance not provided 2012-07-13 no assertion criteria provided research Converted during submission to Uncertain significance.
CSER_CC_NCGL; University of Washington Medical Center RCV000148636 SCV000190351 uncertain significance Colorectal cancer, non-polyposis 2014-06-01 no assertion criteria provided research
Color RCV000115510 SCV000910730 likely benign Hereditary cancer-predisposing syndrome 2016-03-04 criteria provided, single submitter clinical testing
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000076263 SCV000257654 uncertain significance Lynch syndrome 2015-06-05 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000765667 SCV000897009 uncertain significance Lynch syndrome I; Turcot syndrome; Muir-Torré syndrome 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000034553 SCV000149419 uncertain significance not provided 2018-02-13 criteria provided, single submitter clinical testing This variant is denoted MSH2 c.1748A>G at the cDNA level, p.Asn583Ser (N583S) at the protein level, and results in the change of an Asparagine to a Serine (AAT>AGT). This variant has been observed in at least two individuals with suspected Lynch syndrome and in at least three individuals with a history of breast and/or ovarian cancer (Wagner 2003, Chao 2008, Pal 2012, Caminsky 2016, Maxwell 2016). Importantly, one of the probands with suspected Lynch syndrome also carried a pathogenic MLH1 variant (Wagner 2003). This variant was also observed in 1/572 individuals with atherosclerosis, with no specific information about cancer history (Johnston 2012). MSH2 Asn583Ser was observed at an allele frequency of 0.016% (4/24012) in individuals of African ancestry in large population cohorts (Lek 2016). This variant is located in the Lever domain as well as the region of interaction with MSH6 and MSH3 (Guerrette 1998, Lutzen 2008, Kansikas 2011). In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether MSH2 Asn583Ser is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
GeneKor MSA RCV000115510 SCV000822047 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-01 criteria provided, single submitter clinical testing
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000076263 SCV000107284 uncertain significance Lynch syndrome 2013-09-05 reviewed by expert panel research Insufficient evidence
Invitae RCV000524358 SCV000262297 likely benign Hereditary nonpolyposis colon cancer 2017-12-18 criteria provided, single submitter clinical testing
PreventionGenetics RCV000034553 SCV000806011 uncertain significance not provided 2018-01-10 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000212608 SCV000601439 uncertain significance not specified 2017-02-23 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.