ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.339G>A (p.Lys113=) (rs35898375)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 20
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000030252 SCV000107598 no known pathogenicity Lynch syndrome 2013-09-05 reviewed by expert panel research Synonymous variant with no effect on splicing, MAF 0.01-1% & >3 MSS/MSH2 IHC normal CRC tumours. Multifactorial likelihood analysis posterior probability <0.001
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000202152 SCV000110276 benign not specified 2018-03-15 criteria provided, single submitter clinical testing
Invitae RCV001081843 SCV000153878 benign Hereditary nonpolyposis colorectal neoplasms 2020-12-06 criteria provided, single submitter clinical testing
GeneDx RCV000202152 SCV000170336 benign not specified 2013-10-24 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
CSER _CC_NCGL, University of Washington RCV000030252 SCV000212175 benign Lynch syndrome 2015-03-11 criteria provided, single submitter research
Ambry Genetics RCV000157761 SCV000212736 benign Hereditary cancer-predisposing syndrome 2014-11-18 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
PreventionGenetics,PreventionGenetics RCV000202152 SCV000303164 benign not specified criteria provided, single submitter clinical testing
Color Health, Inc RCV000157761 SCV000537397 benign Hereditary cancer-predisposing syndrome 2014-12-08 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV000202152 SCV000595827 benign not specified 2017-09-20 criteria provided, single submitter clinical testing
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000606468 SCV000744266 benign Lynch syndrome I 2015-09-21 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory,VU University Medical Center Amsterdam RCV000606468 SCV000745631 benign Lynch syndrome I 2015-11-08 criteria provided, single submitter clinical testing
Mendelics RCV000606468 SCV001135698 likely benign Lynch syndrome I 2019-05-28 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000524404 SCV001152271 likely benign not provided 2018-07-01 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000202152 SCV001156594 benign not specified 2019-05-17 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000606468 SCV001304222 uncertain significance Lynch syndrome I 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000030252 SCV000052919 benign Lynch syndrome 2012-10-01 no assertion criteria provided clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000202152 SCV000257185 benign not specified no assertion criteria provided research
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000030252 SCV000592461 likely benign Lynch syndrome no assertion criteria provided clinical testing The MSH2 p.Lys113Lys variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. The variant was identified in the literature in 5 of 744 proband chromosomes (frequency 0.007) from individuals with colon cancer and was absent in 180 control chromosomes evaluated from these studies (Liu 1998, Palicio 2002, Pastrello 2011, Tournier 2008). The variant was also identified in dbSNP (ID: rs35898375) “With probable-non-pathogenic allele”, “Mismatch Repair Genes Variant Database”, “InSiGHT Colon Cancer Database”, “MMR Gene Unclassified Variants Database” and UMD (11X as a neutral variant). Within the UMD listing, the variant is listed to co-occur with a known pathogenic mutation in MSH2 (c.1058del, p.Lys353ArgfsX4), increasing the likelihood that this variant does not have clinical importance. Pastrello (2011) found this variant in three families that were Amsterdam-like or met Amsterdam I criteria; in all three cases the variant was found to co-occur with a pathogenic mutation in either MLH1 or MSH2. In one of the three families, the variant was determined to be in trans with a pathogenic MSH2 mutation, and the tumour showed loss of heterozygosity of the p.Lys113Lys variant allele, further increasing the likelihood of the variant not having clinical importance. In addition, one functional assay demonstrated no effect of this variant on splicing, which was concordant with analysis of patient RNA (Tournier 2008). Finally, the variant was reported in the 1000 Genomes project with a frequency of 0.002 and in the ClinSeq project with a frequency of 0.007, increasing the likelihood that this may be a low frequency benign variant in certain populations of origin. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as predicted benign.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000606468 SCV000734197 likely benign Lynch syndrome I no assertion criteria provided clinical testing
True Health Diagnostics RCV000157761 SCV000788036 benign Hereditary cancer-predisposing syndrome 2017-10-11 no assertion criteria provided 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.