ClinVar Miner

Submissions for variant NM_001048174.2(MUTYH):c.632_637delinsCAGCTGCT (p.Val211fs)

dbSNP: rs1064793197
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000482643 SCV000565256 pathogenic not provided 2017-11-22 criteria provided, single submitter clinical testing This combined deletion and insertion is denoted MUTYH c.716_721delTAGCACinsCAGCTGCT at the cDNA level and p.Val239AlafsX28 (V239AfsX28) at the protein level. The surrounding sequence is AACG[delTAGCACinsCAGCTGCT]GGGT. The variant causes a frameshift, which changes a Valine to an Alanine at codon 239, and creates a premature stop codon at position 28 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Based on currently available evidence, we consider this to be a likely pathogenic variant.
Labcorp Genetics (formerly Invitae), Labcorp RCV000792421 SCV000931719 pathogenic Familial adenomatous polyposis 2 2018-09-20 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in MUTYH are known to be pathogenic (PMID: 18534194, 20663686). This variant has not been reported in the literature in individuals with MUTYH-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Val239Alafs*28) in the MUTYH gene. It is expected to result in an absent or disrupted protein product.
Ambry Genetics RCV002374880 SCV002665592 pathogenic Hereditary cancer-predisposing syndrome 2020-06-15 criteria provided, single submitter clinical testing The c.716_721delTAGCACinsCAGCTGCT pathogenic mutation, located in coding exon 9 of the MUTYH gene, results from the deletion of 6 nucleotides and insertion of 8 nucleotides causing a translational frameshift with a predicted alternate stop codon (p.V239Afs*28). This mutation was observed in a cohort of patients with biallelic MUTYH mutations (Sutcliffe EG et al. Fam. Cancer 2019 04;18:203-209). In addition to the clinical data presented in the literature, 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.

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.