ClinVar Miner

Submissions for variant NM_000249.3(MLH1):c.652T>C (p.Ser218Pro) (rs750650349)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000475778 SCV000543604 uncertain significance Hereditary nonpolyposis colon cancer 2018-08-05 criteria provided, single submitter clinical testing This sequence change replaces serine with proline at codon 218 of the MLH1 protein (p.Ser218Pro). The serine residue is weakly conserved and there is a moderate physicochemical difference between serine and proline. This variant is present in population databases (rs750650349, ExAC 0.009%). This variant has not been reported in the literature in individuals with MLH1-related disease. ClinVar contains an entry for this variant (Variation ID: 405413). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
Ambry Genetics RCV000564654 SCV000662013 uncertain significance Hereditary cancer-predisposing syndrome 2017-12-15 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Mendelics RCV000708916 SCV000838002 uncertain significance Lynch syndrome 2018-07-02 criteria provided, single submitter clinical testing
Color RCV000564654 SCV000911477 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-18 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.