ClinVar Miner

Submissions for variant NM_001048171.1(MUTYH):c.347-7C>A (rs863224698)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000195589 SCV000254712 uncertain significance MYH-associated polyposis 2020-07-20 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 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: 216521). 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.
GeneDx RCV000235223 SCV000294031 uncertain significance not provided 2016-03-02 criteria provided, single submitter clinical testing This variant is denoted MUTYH c.389-7C>A or IVS4-7C>A and consists of a C>A nucleotide substitution at the -7 position of intron 4 of the MUTYH gene. Multiple in silico models predict this variant to damage the nearby natural acceptor site and to possibly cause abnormal gene splicing; however, in the absence of RNA or functional studies, the actual effect of this variant is unknown. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. MUTYH c.389-7C>A was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. The cytosine (C) nucleotide that is altered is not conserved. Based on currently available information, it is unclear whether MUTYH c.389-7C>A is pathogenic or benign. We consider it to be a variant of uncertain significance. Of note, MUTYH-Associated Polyposis (MAP) is a recessive condition associated with two pathogenic variants on opposite chromosomes in MUTYH.
Illumina Clinical Services Laboratory,Illumina RCV000195589 SCV000357904 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.
Color Health, Inc RCV000580780 SCV000685624 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-29 criteria provided, single submitter clinical testing
Counsyl RCV000195589 SCV000798917 likely benign MYH-associated polyposis 2018-03-28 criteria provided, single submitter clinical testing

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