ClinVar Miner

Submissions for variant NM_001281492.1(MSH6):c.1511_1512del (p.Thr503_Leu504insTer) (rs267608082)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000074696 SCV000107901 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation resulting in a stop codon
Invitae RCV000524125 SCV000551072 pathogenic Hereditary nonpolyposis colorectal neoplasms 2020-09-30 criteria provided, single submitter clinical testing This sequence change deletes 2 nucleotides from exon 4 of the MSH6 mRNA (c.1901_1902delTG), causing a frameshift at codon 634. This creates a premature translational stop signal (p.Leu634*) and is expected to result in an absent or disrupted protein product. Loss-of-function variants in MSH6 are known to be pathogenic. This particular variant has been reported in the literature in a family affected with endometrial cancer and other Lynch syndrome-associated cancers (PMID: 12732731, 15098177). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV001013617 SCV001174225 pathogenic Hereditary cancer-predisposing syndrome 2017-12-28 criteria provided, single submitter clinical testing The c.1901_1902delTG pathogenic mutation, located in coding exon 4 of the MSH6 gene, results from a deletion of two nucleotides at nucleotide positions 1901 to 1902, causing a translational frameshift with a predicted alternate stop codon (p.L634*). This mutation has been reported in a proband with MSI-high endometrial cancer diagnosed at age 58 (Goodfellow PJ et al. Proc. Natl. Acad. Sci. U.S.A., 2003 May;100:5908-13). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001284179 SCV001469820 pathogenic not provided 2020-01-03 criteria provided, single submitter clinical testing The variant creates a premature stop codon, and is therefore predicted to result in the loss of a functional protein. Found in at least one patient with expected phenotype for this gene, and not found in general population data. Segregation with disease in affected individuals from a single family.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001284179 SCV001549372 uncertain significance not provided no assertion criteria provided clinical testing

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