ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.3514_3515AG[1] (p.Arg1172fs) (rs398123232)

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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 RCV000162479 SCV000212852 pathogenic Hereditary cancer-predisposing syndrome 2018-01-22 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000078316 SCV000110160 pathogenic not provided 2013-01-21 criteria provided, single submitter clinical testing
GeneDx RCV000078316 SCV000568727 pathogenic not provided 2015-11-19 criteria provided, single submitter clinical testing This deletion of 2 nucleotides in MSH6 is denoted c.3516_3517delAG at the cDNA level and p.Arg1172SerfsX4(R1172SfsX4) at the protein level. The normal sequence, with the bases that are deleted in braces, is ATAG[AG]TGTT. The deletion causes a frameshift, which changes an Arginine to a Serine at codon 1172, and creates a premature stop codon at position 4 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. MSH6 c.3516_3517delAG has been reported in association with Lynch syndrome (Baglietto 2010). We consider this variant to be pathogenic.
GeneKor MSA RCV000162479 SCV000821741 pathogenic Hereditary cancer-predisposing syndrome 2018-08-01 criteria provided, single submitter clinical testing
Invitae RCV000200371 SCV000255264 pathogenic Hereditary nonpolyposis colon cancer 2017-12-27 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg1172Serfs*4) in the MSH6 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in the literature in a family with multiple-case colorectal cancer or Lynch syndrome (PMID: 20028993). This variant is also known as c.3516_3517delAG (p.R1172fs) in the literature. ClinVar contains an entry for this variant (Variation ID: 92578). Loss-of-function variants in MSH6 are known to be pathogenic (PMID: 24362816, 18269114). For these reasons, this variant has been classified as Pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000078316 SCV000601577 pathogenic not provided 2017-05-05 criteria provided, single submitter clinical testing

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