ClinVar Miner

Submissions for variant NM_001128425.1(MUTYH):c.690G>A (p.Gln230=) (rs199989617)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000567080 SCV000666478 likely pathogenic Hereditary cancer-predisposing syndrome 2016-04-28 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Last nucleotide of exon with predicted splicing impact in agreement,Detected in individual(s) satisfying established diagnostic criteria for classic disease in trans with a mutation or mutation is homozygous,Other data supporting pathogenic classification
Color RCV000567080 SCV000913515 likely pathogenic Hereditary cancer-predisposing syndrome 2018-06-09 criteria provided, single submitter clinical testing
Invitae RCV000702233 SCV000831079 likely pathogenic MYH-associated polyposis 2018-09-04 criteria provided, single submitter clinical testing This sequence change affects codon 230 of the MUTYH mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the MUTYH protein. This variant also falls at the last nucleotide of exon 8 of the MUTYH coding sequence, which is part of the consensus splice site for this exon. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with MUTYH-associated polyposis and has been observed on the opposite chromosome (in trans) from a pathogenic variant in at least two of these individuals (PMID: 19732775, 25559809). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. ClinVar contains an entry for this variant (Variation ID: 481804). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). An experimental study has shown that this silent change can results in skipping of exon 8 or exons 8-9 of the MUTYH mRNA. (PMID: 18515411). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759166 SCV000888323 likely pathogenic not provided 2018-03-27 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.