ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.2718A>G (p.Ile906Met)

gnomAD frequency: 0.00001  dbSNP: rs876659835
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
Ambry Genetics RCV000216683 SCV000276710 uncertain significance Hereditary cancer-predisposing syndrome 2024-02-28 criteria provided, single submitter clinical testing The p.I906M variant (also known as c.2718A>G), located in coding exon 16 of the MSH2 gene, results from an A to G substitution at nucleotide position 2718. The isoleucine at codon 906 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV002229281 SCV000548285 likely benign Hereditary nonpolyposis colorectal neoplasms 2023-10-28 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000216683 SCV001345630 uncertain significance Hereditary cancer-predisposing syndrome 2023-05-17 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with methionine at codon 906 of the MSH2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with MSH2-related disorders in the literature. This variant has been identified in 1/31414 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.
All of Us Research Program, National Institutes of Health RCV003997983 SCV004829909 uncertain significance Lynch syndrome 2023-06-08 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with methionine at codon 906 of the MSH2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/31414 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.

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.