ClinVar Miner

Submissions for variant NM_001048171.1(MUTYH):c.1452G>C (p.Gln484His) (rs587782794)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000132344 SCV000187433 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-27 criteria provided, single submitter clinical testing The p.Q498H variant (also known as c.1494G>C), located in coding exon 15 of the MUTYH gene, results from a G to C substitution at nucleotide position 1494. The glutamine at codon 498 is replaced by histidine, an amino acid with highly similar properties. This alteration was previously reported in a 42 year-old with rectal cancer and no family history of colorectal cancer (Görgens H et al. J Mol Diagn 2006 May; 8(2):178-82). This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV000198891 SCV000254705 uncertain significance MYH-associated polyposis 2020-09-02 criteria provided, single submitter clinical testing This sequence change replaces glutamine with histidine at codon 498 of the MUTYH protein (p.Gln498His). The glutamine residue is weakly conserved and there is a small physicochemical difference between glutamine and histidine. This variant is present in population databases (rs587782794, ExAC 0.002%). This variant has been reported in an individual affected with rectal cancer (PMID: 16645203). ClinVar contains an entry for this variant (Variation ID: 142884). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Benign; Align-GVGD: Class C0). 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.
Counsyl RCV000198891 SCV000792268 uncertain significance MYH-associated polyposis 2017-06-13 criteria provided, single submitter clinical testing
Color Health, Inc RCV000132344 SCV000903807 uncertain significance Hereditary cancer-predisposing syndrome 2019-04-04 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000198891 SCV001257604 uncertain significance MYH-associated polyposis 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
GeneDx RCV001558131 SCV001780016 uncertain significance not provided 2020-07-13 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Observed in individuals with a personal or family history of early-onset rectal cancer (Grgens 2006); This variant is associated with the following publications: (PMID: 24834277, 21061173, 16645203, 25525159)

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