ClinVar Miner

Submissions for variant NM_001128425.1(MUTYH):c.389-6C>T (rs376600220)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000441283 SCV000524583 likely benign not specified 2017-08-17 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV000471644 SCV000545713 uncertain significance MYH-associated polyposis 2020-09-23 criteria provided, single submitter clinical testing This sequence change falls in intron 4 of the MUTYH gene. It does not directly change the encoded amino acid sequence of the MUTYH protein. This variant is present in population databases (rs376600220, ExAC 0.009%). This variant has not been reported in the literature in individuals with MUTYH-related disease. ClinVar contains an entry for this variant (Variation ID: 383957). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Color Health, Inc RCV000771496 SCV000903981 likely benign Hereditary cancer-predisposing syndrome 2017-12-03 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000441283 SCV000917809 uncertain significance not specified 2018-09-28 criteria provided, single submitter clinical testing Variant summary: MUTYH c.389-6C>T alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 3.7e-05 in 246170 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.389-6C>T in individuals affected with MUTYH-associated Polyposis and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as likely benign, and one laboratory classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001284666 SCV001470573 uncertain significance not provided 2020-01-10 criteria provided, single submitter clinical testing

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