ClinVar Miner

Submissions for variant NM_001048171.1(MUTYH):c.1144+9A>T (rs587780742)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000123140 SCV000166442 likely benign MYH-associated polyposis 2020-12-03 criteria provided, single submitter clinical testing
Ambry Genetics RCV000129212 SCV000183962 likely benign Hereditary cancer-predisposing syndrome 2015-09-02 criteria provided, single submitter clinical testing Insufficient or conflicting evidence;Rare (0.1%) in general population databases (dbsnp, esp, 1000 genomes)
Illumina Clinical Services Laboratory,Illumina RCV000123140 SCV000357893 uncertain significance MYH-associated polyposis 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Counsyl RCV000123140 SCV000487386 likely benign MYH-associated polyposis 2016-10-28 criteria provided, single submitter clinical testing
GeneDx RCV000431410 SCV000513736 benign not specified 2015-03-19 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.
PreventionGenetics,PreventionGenetics RCV000589767 SCV000806338 likely benign not provided 2017-04-12 criteria provided, single submitter clinical testing
Color Health, Inc RCV000129212 SCV000910733 likely benign Hereditary cancer-predisposing syndrome 2016-06-20 criteria provided, single submitter clinical testing
Mendelics RCV000123140 SCV001135252 likely benign MYH-associated polyposis 2019-05-28 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000431410 SCV001363474 uncertain significance not specified 2019-11-08 criteria provided, single submitter clinical testing Variant summary: MUTYH c.1186+9A>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. 5/5 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 0.00011 in 249362 control chromosomes, predominantly at a frequency of 0.00021 within the Non-Finnish European subpopulation in the gnomAD database. This frequency is not higher than expected for a pathogenic variant in MUTYH causing MUTYH-associated Polyposis (0.00021 vs 0.0046), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.1186+9A>T in individuals affected with MUTYH-associated Polyposis and no experimental evidence demonstrating its impact on protein function have been reported in the literature. Seven ClinVar submitters (evaluation after 2014) cite the variant as benign/likely benign (n=5) and as uncertain significance (n=2). Based on the evidence outlined above, the variant was classified as uncertain significance.

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