ClinVar Miner

Submissions for variant NM_001128425.1(MUTYH):c.1323G>A (p.Glu441=) (rs587782564)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131785 SCV000186834 likely benign Hereditary cancer-predisposing syndrome 2020-06-23 criteria provided, single submitter clinical testing RNA Studies
Invitae RCV000462220 SCV000545729 uncertain significance MYH-associated polyposis 2019-03-13 criteria provided, single submitter clinical testing This sequence change affects codon 441 of the MUTYH mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the MUTYH protein. This variant also falls at the last nucleotide of exon 13 of the MUTYH coding sequence, which is part of the consensus splice site for this exon. This variant is present in population databases (rs587782564, ExAC 0.01%). This variant has not been reported in the literature in individuals with MUTYH-related disease. ClinVar contains an entry for this variant (Variation ID: 142583). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing, 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 RCV000579114 SCV000680806 uncertain significance not provided 2017-10-02 criteria provided, single submitter clinical testing This variant is denoted MUTYH c.1323G>A at the DNA level. This variant is silent at the coding level, preserving a Glutamic Acid at codon 441. It is not predicted to cause abnormal splicing. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. This variant was not observed at a significant allele frequency in large population cohorts (Lek 2016). The nucleotide which is altered, a guanine (G) at base 1323, is conserved across species. Based on currently available information, it is unclear whether MUTYH c.1323G>A is a pathogenic or benign variant. 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.
Color Health, Inc RCV000131785 SCV001352097 uncertain significance Hereditary cancer-predisposing syndrome 2019-10-28 criteria provided, single submitter clinical testing

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