ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.3029C>T (p.Thr1010Ile)

dbSNP: rs768925694
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000570481 SCV000676341 uncertain significance Hereditary cancer-predisposing syndrome 2021-12-09 criteria provided, single submitter clinical testing The p.T1010I variant (also known as c.3029C>T), located in coding exon 4 of the MSH6 gene, results from a C to T substitution at nucleotide position 3029. The threonine at codon 1010 is replaced by isoleucine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
University of Washington Department of Laboratory Medicine, University of Washington RCV000758675 SCV000887446 likely benign Lynch syndrome 2018-05-01 criteria provided, single submitter clinical testing MSH6 NM_000179.2:c.3029C>T has a 2.2% probability of pathogenicity based on combining prior probability from public data with a likelihood ratio of 0.20 to 1, generated from evidence of seeing this as a somatic mutation in a tumor without loss of heterozygosity at the MSH6 locus. See Shirts et al 2018, PMID 29887214.
Color Diagnostics, LLC DBA Color Health RCV000570481 SCV000904026 uncertain significance Hereditary cancer-predisposing syndrome 2018-11-25 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001327550 SCV001518630 likely benign Hereditary nonpolyposis colorectal neoplasms 2024-02-12 criteria provided, single submitter clinical testing
Baylor Genetics RCV004568234 SCV005054875 uncertain significance Endometrial carcinoma 2024-03-05 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV000758675 SCV005429380 uncertain significance Lynch syndrome 2024-04-25 criteria provided, single submitter clinical testing This missense variant replaces threonine with isoleucine at codon 1010 of the MSH6 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 MSH6-related disorders in the literature. This variant has been identified in 1/217938 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.

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