ClinVar Miner

Submissions for variant NM_001128425.1(MUTYH):c.690+1G>T (rs878854193)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000230698 SCV000285961 likely pathogenic MYH-associated polyposis 2018-08-26 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 8 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 not been reported in the literature in individuals with MUTYH-related disease. ClinVar contains an entry for this variant (Variation ID: 238352). 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: 18534194, 20663686). 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.
GeneDx RCV000482610 SCV000571605 likely pathogenic not provided 2016-09-07 criteria provided, single submitter clinical testing This variant is denoted MUTYH c.690+1G>T or IVS8+1G>T and consists of a G>T nucleotide substitution at the +1 position of intron 8 of the MUTYH gene. Although this variant destroys a canonical splice acceptor site and is predicted to cause abnormal splicing of exon 8, the skipping of exon 8 is predicted to be an in-frame event. While this particular variant has not, to our knowledge, been published in the literature, a nearby exonic variant, MUTYH c.690G>A, has been shown to result in skipping of exon 8 (Dallosso 2008). Importantly, Dellosso et al. (2008) reported that MUTYH c.690G>A has occurred in trans with MUTYH Tyr179Cys, one of the two common MUTYH pathogenic variants, in two individuals presenting with a phenotype consistent with MUTYH-Associated Polyposis (MAP), thus supporting that the skipping of exon 8 is deleterious. Based on the currently available information, we consider MUTYH c.690+1G>T to be a likely pathogenic variant.

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