ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.2992T>A (p.Ser998Thr)

gnomAD frequency: 0.00001  dbSNP: rs730881800
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000160685 SCV000211306 uncertain significance not provided 2021-01-14 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in an individual with a personal history of colorectal cancer in published literature (Limburg 2011); This variant is associated with the following publications: (PMID: 30798936, 21056691, 23621914)
Invitae RCV000168112 SCV000218768 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2024-01-31 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with threonine, which is neutral and polar, at codon 998 of the MSH6 protein (p.Ser998Thr). This variant is present in population databases (rs730881800, gnomAD 0.003%). This missense change has been observed in individual(s) with colorectal cancer (PMID: 21056691). ClinVar contains an entry for this variant (Variation ID: 182639). An algorithm developed specifically for the MSH6 gene suggests that this missense change is likely to be deleterious (PMID: 23621914). 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.
Color Diagnostics, LLC DBA Color Health RCV000579908 SCV000685345 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-30 criteria provided, single submitter clinical testing
Counsyl RCV000662434 SCV000784890 uncertain significance Lynch syndrome 5 2017-01-27 criteria provided, single submitter clinical testing
Ambry Genetics RCV000579908 SCV001178986 uncertain significance Hereditary cancer-predisposing syndrome 2022-12-07 criteria provided, single submitter clinical testing The p.S998T variant (also known as c.2992T>A), located in coding exon 4 of the MSH6 gene, results from a T to A substitution at nucleotide position 2992. The serine at codon 998 is replaced by threonine, an amino acid with similar properties. This variant was observed in a female patient diagnosed with rectal cancer at age 45 (Limburg PJ et al, 2011 Jun;9:497-502). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden RCV000160685 SCV002010100 uncertain significance not provided 2021-11-03 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV000662434 SCV004018962 uncertain significance Lynch syndrome 5 2023-03-29 criteria provided, single submitter clinical testing This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk.
All of Us Research Program, National Institutes of Health RCV003998498 SCV004834411 uncertain significance Lynch syndrome 2023-05-15 criteria provided, single submitter clinical testing

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