ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.3524C>T (p.Thr1175Ile)

gnomAD frequency: 0.00002  dbSNP: rs369583604
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000484936 SCV000572158 uncertain significance not provided 2023-09-20 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; This variant is associated with the following publications: (PMID: 17531815, 21120944)
Ambry Genetics RCV000573926 SCV000669934 uncertain significance Hereditary cancer-predisposing syndrome 2024-02-07 criteria provided, single submitter clinical testing The p.T1175I variant (also known as c.3524C>T), located in coding exon 6 of the MSH6 gene, results from a C to T substitution at nucleotide position 3524. The threonine at codon 1175 is replaced by isoleucine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV000706792 SCV000835862 likely benign Hereditary nonpolyposis colorectal neoplasms 2025-01-30 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000573926 SCV001353080 uncertain significance Hereditary cancer-predisposing syndrome 2019-08-15 criteria provided, single submitter clinical testing This missense variant replaces threonine with isoleucine at codon 1175 of the MSH6 protein. Computational prediction tools and conservation analyses suggest that this variant may have deleterious impact on the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 4/282662 chromosomes in the general population by the Genome Aggregation Database (gnomAD). 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.
Sema4, Sema4 RCV000573926 SCV002528039 uncertain significance Hereditary cancer-predisposing syndrome 2022-02-08 criteria provided, single submitter curation
All of Us Research Program, National Institutes of Health RCV004003383 SCV004835084 uncertain significance Lynch syndrome 2024-06-11 criteria provided, single submitter clinical testing This missense variant replaces threonine with isoleucine at codon 1175 of the MSH6 protein. Computational prediction tools and conservation analyses suggest that this variant may have deleterious impact on the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 4/282662 chromosomes in the general population by the Genome Aggregation Database (gnomAD). 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.
Baylor Genetics RCV004568202 SCV005054957 uncertain significance Endometrial carcinoma 2024-01-23 criteria provided, single submitter clinical testing

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