ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.182A>C (p.Gln61Pro) (rs587779113)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001703978 SCV000730543 likely benign not provided 2020-10-26 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 16995940, 17720936, 26333163, 25133505, 18383312, 20176959, 31159747, 32957588)
Counsyl RCV000662761 SCV000785555 uncertain significance Lynch syndrome I 2017-09-13 criteria provided, single submitter clinical testing
GeneKor MSA RCV000708715 SCV000822049 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-01 criteria provided, single submitter clinical testing
Color Health, Inc RCV000708715 SCV000908272 uncertain significance Hereditary cancer-predisposing syndrome 2020-07-22 criteria provided, single submitter clinical testing This missense variant replaces glutamine with proline at codon 61 of the MSH2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. Experimental studies have reported this variant protein to be functional in yeast mutator and protein binding assays (PMID: 17720936, 20176959). This variant has been reported in an individual affected with ovarian and colorectal cancer (PMID: 25133505). This variant has been identified in 1/232376 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000708715 SCV001173915 likely benign Hereditary cancer-predisposing syndrome 2020-03-04 criteria provided, single submitter clinical testing In silico models in agreement (benign);Other data supporting benign classification
Invitae RCV001218170 SCV001390042 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2020-08-31 criteria provided, single submitter clinical testing This sequence change replaces glutamine with proline at codon 61 of the MSH2 protein (p.Gln61Pro). The glutamine residue is weakly conserved and there is a moderate physicochemical difference between glutamine and proline. This variant is present in population databases (rs587779113, ExAC 0.002%). This variant has been observed in individual(s) with clinical features of Lynch syndrome (PMID: 25133505, Invitae). ClinVar contains an entry for this variant (Variation ID: 90798). Experimental studies have shown that this variant does not substantially affect MSH2 protein function (PMID: 17720936, 20176959). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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.