ClinVar Miner

Submissions for variant NM_001128425.1(MUTYH):c.389-1G>C (rs372267274)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 10
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000221410 SCV000278764 pathogenic Hereditary cancer-predisposing syndrome 2018-04-24 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations at the canonical donor/acceptor sites (+/- 1, 2) without splicing assay data in support of pathogenicity,Other strong data supporting pathogenic classification ,Detected in individual(s) satisfying established diagnostic criteria for classic disease in trans with a mutation or mutation is homozygous
Color RCV000221410 SCV000685623 likely pathogenic Hereditary cancer-predisposing syndrome 2018-09-23 criteria provided, single submitter clinical testing
Counsyl RCV000230931 SCV000487337 pathogenic MYH-associated polyposis 2016-02-26 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000230931 SCV000592682 pathogenic MYH-associated polyposis 2015-03-02 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000763342 SCV000894024 pathogenic MYH-associated polyposis; Pilomatrixoma; Neoplasm of stomach 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000478994 SCV000568584 pathogenic not provided 2018-08-29 criteria provided, single submitter clinical testing This variant is denoted MUTYH c.389-1G>C or IVS4-1G>C and consists of a G>C nucleotide substitution at the -1 position of intron 4 of the MUTYH gene. This variant destroys a canonical splice acceptor site and is predicted to cause abnormal gene splicing, leading to either an abnormal message that is subject to nonsense-mediated mRNA decay or to an abnormal protein product. This variant, also reported as c.347-1G>C using alternate nomenclature, has been detected in trans with a second pathogenic MUTYH variant in several individuals with multiple colorectal adenomas (Isidro 2004, Filipe 2009, Torrezan 2013). Based on the current evidence, we consider this variant to be pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000586609 SCV000697693 pathogenic MUTYH-associated polyposis 2016-10-28 criteria provided, single submitter clinical testing Variant summary: The MUTYH c.389-1G>C variant involves the alteration of a conserved intronic nucleotide. One in silico tool predicts a damaging outcome for this variant. 5/5 splice prediction tools predict that this variant abolishes the 3' splicing acceptor site in intron 4. This variant is absent in 121386 control chromosomes, however, has been reported in numerous MAP patients. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Invitae RCV000230931 SCV000285947 pathogenic MYH-associated polyposis 2018-12-18 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 4 of the MUTYH gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed as to be homozygous and in combination with another pathogenic MUTYH variant in individuals with colorectal polyposis (PMID: 15366000, 17949294, 23561487, Invitae). This variant is also known as c.347-1G>C in the literature. ClinVar contains an entry for this variant (Variation ID: 234229). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in MUTYH are known to be pathogenic (PMID: 20663686, 18534194). For these reasons, this variant has been classified as Pathogenic.
Mendelics RCV000230931 SCV000837780 pathogenic MYH-associated polyposis 2018-07-02 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000478994 SCV000888315 pathogenic not provided 2017-12-07 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.