ClinVar Miner

Submissions for variant NM_002439.5(MSH3):c.1655C>T (p.Thr552Ile)

gnomAD frequency: 0.00004  dbSNP: rs749862056
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000798641 SCV000938267 uncertain significance not provided 2025-01-22 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 552 of the MSH3 protein (p.Thr552Ile). This variant is present in population databases (rs749862056, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with MSH3-related conditions. ClinVar contains an entry for this variant (Variation ID: 644672). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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 RCV001012579 SCV001173048 uncertain significance Hereditary cancer-predisposing syndrome 2024-10-14 criteria provided, single submitter clinical testing The p.T552I variant (also known as c.1655C>T), located in coding exon 12 of the MSH3 gene, results from a C to T substitution at nucleotide position 1655. The threonine at codon 552 is replaced by isoleucine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear.
Sema4, Sema4 RCV001012579 SCV002535974 uncertain significance Hereditary cancer-predisposing syndrome 2021-11-17 criteria provided, single submitter curation
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000798641 SCV002774629 uncertain significance not provided 2022-07-08 criteria provided, single submitter clinical testing
Baylor Genetics RCV003461106 SCV004196975 uncertain significance Endometrial carcinoma 2024-03-13 criteria provided, single submitter clinical testing
GeneDx RCV000798641 SCV005325723 uncertain significance not provided 2023-07-03 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Fulgent Genetics, Fulgent Genetics RCV005036156 SCV005666189 uncertain significance Endometrial carcinoma; Familial adenomatous polyposis 4 2024-02-27 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.