ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.2205C>T (p.Ile735=) (rs533553381)

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
GeneDx RCV000212617 SCV000170347 benign not specified 2013-12-27 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.
Ambry Genetics RCV000126821 SCV000212951 likely benign Hereditary cancer-predisposing syndrome 2014-09-16 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000323210 SCV000430933 uncertain significance Lynch syndrome 2016-06-14 criteria provided, single submitter clinical testing
Counsyl RCV000409899 SCV000488353 likely benign Lynch syndrome I 2016-03-08 criteria provided, single submitter clinical testing
Invitae RCV000590738 SCV000559194 benign not provided 2019-03-03 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000212617 SCV000592543 benign not specified 2015-05-20 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000212617 SCV000601460 benign not specified 2017-04-18 criteria provided, single submitter clinical testing
Color RCV000126821 SCV000685022 benign Hereditary cancer-predisposing syndrome 2015-06-11 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000590738 SCV000696238 benign not provided 2016-08-15 criteria provided, single submitter clinical testing Variant summary: The MSH2 c.2205C>T (p.Ile735Ile) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a damaging outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 185/121382 control chromosomes (2 homozygotes), predominantly observed in the South Asian subpopulation at a frequency of 0.0109038 (180/16508). This frequency is about 19 times the estimated maximal expected allele frequency of a pathogenic MSH2 variant (0.0005683), suggesting this is likely a benign polymorphism found primarily in the populations of South Asian origin. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign/likely benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. One internal sample also carried a disease variant in BRCA1 c.3869_3870delAA, further suppporting the benign classification. Taken together, this variant is classified as benign.
PreventionGenetics,PreventionGenetics RCV000212617 SCV000806027 benign not specified 2017-07-06 criteria provided, single submitter clinical testing
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000212617 SCV000691910 likely benign not specified no assertion criteria provided clinical testing
True Health Diagnostics RCV000126821 SCV000805269 likely benign Hereditary cancer-predisposing syndrome 2018-05-09 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.