ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.335C>T (p.Ser112Phe) (rs769215192)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000235804 SCV000293282 uncertain significance not provided 2017-11-16 criteria provided, single submitter clinical testing This variant is denoted MSH2 c.335C>T at the cDNA level, p.Ser112Phe (S112F) at the protein level, and results in the change of a Serine to a Phenylalanine (TCC>TTC). This variant has not, to our knowledge, been published in the literature as being pathogenic or benign. MSH2 Ser112Phe was not observed in large population cohorts (Lek 2016). Since Serine and Phenylalanine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. MSH2 Ser112Phe is located in the mismatch binding domain (Lutzen 2008, Kansikas 2011). In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Based on currently available evidence, it is unclear whether MSH2 Ser112Phe is pathogenic or benign. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV001020082 SCV001181513 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-03 criteria provided, single submitter clinical testing Insufficient evidence
Invitae RCV001211169 SCV001382694 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2019-09-17 criteria provided, single submitter clinical testing This sequence change replaces serine with phenylalanine at codon 112 of the MSH2 protein (p.Ser112Phe). The serine residue is moderately conserved and there is a large physicochemical difference between serine and phenylalanine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with MSH2-related conditions. ClinVar contains an entry for this variant (Variation ID: 246010). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; 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.

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.