ClinVar Miner

Submissions for variant NM_001048174.2(MUTYH):c.694C>T (p.Gln232Ter)

gnomAD frequency: 0.00001  dbSNP: rs773087549
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000235928 SCV000293892 likely pathogenic not provided 2016-02-01 criteria provided, single submitter clinical testing This variant is denoted MUTYH c.778C>T at the cDNA level and p.Gln260Ter (Q260X) at the protein level. The substitution creates a nonsense variant, which changes a Glutamine to a premature stop codon (CAG>TAG) , and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Although this variant has not, to our knowledge, been reported in the literature, it is considered likely pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV001222430 SCV001394528 pathogenic Familial adenomatous polyposis 2 2023-09-27 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln260*) in the MUTYH gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MUTYH are known to be pathogenic (PMID: 18534194, 20663686). This variant is present in population databases (rs773087549, gnomAD 0.006%). This premature translational stop signal has been observed in individual(s) with colorectal polyposis (PMID: 29330641). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 246369). For these reasons, this variant has been classified as Pathogenic.
Revvity Omics, Revvity RCV001222430 SCV003820322 pathogenic Familial adenomatous polyposis 2 2023-01-17 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV001222430 SCV004843350 pathogenic Familial adenomatous polyposis 2 2023-12-13 criteria provided, single submitter clinical testing This variant changes 1 nucleotide in exon 9 of the MUTYH gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been observed with a co-occurring pathogenic variant in an individual affected with over 100 colorectal polyps (PMID: 29330641), indicating that this variant contributes to disease. This variant has been identified in 2/250372 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of MUTYH function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.

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