ClinVar Miner

Submissions for variant NM_001048174.2(MUTYH):c.914-1G>T

dbSNP: rs2149130255
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001385504 SCV001585382 pathogenic Familial adenomatous polyposis 2 2021-10-06 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant is also known as c.956-1G>T. Disruption of this splice site has been observed in individual(s) with MUTYH-associated polyposis (PMID: 17949294, 27829682). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (ExAC no frequency). This sequence change affects an acceptor splice site in intron 11 of the MUTYH gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site 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).
Color Diagnostics, LLC DBA Color Health RCV001523926 SCV001733666 likely pathogenic Hereditary cancer-predisposing syndrome 2020-06-23 criteria provided, single submitter clinical testing This variant causes a G to T nucleotide substitution at the -1 position of intron 11 of the MUTYH gene. Splice site prediction tools predict that this variant may have a significant impact on RNA splicing. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in individuals with MUTYH-associated polyposis or colorectal cancer plus colorectal polyps (PMID: 17949294, 27705013, 27829682). This variant has not been identified 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 Likely Pathogenic.

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