ClinVar Miner

Submissions for variant NM_001048171.1(MUTYH):c.451G>A (p.Ala151Thr) (rs201103359)

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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 RCV000165474 SCV000216205 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-09 criteria provided, single submitter clinical testing The p.A165T variant (also known as c.493G>A), located in coding exon 6 of the MUTYH gene, results from a G to A substitution at nucleotide position 493. The alanine at codon 165 is replaced by threonine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV000228243 SCV000285952 uncertain significance MYH-associated polyposis 2020-08-09 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 165 of the MUTYH protein (p.Ala165Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs201103359, ExAC 0.05%). This variant has been observed in individual(s) undergoing multigene testing for hereditary cancer (PMID: 31159747). ClinVar contains an entry for this variant (Variation ID: 185959). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Color Health, Inc RCV000165474 SCV000685633 uncertain significance Hereditary cancer-predisposing syndrome 2019-10-02 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000590519 SCV000697698 uncertain significance not provided 2016-11-25 criteria provided, single submitter clinical testing Variant summary: The c.493G>A (p.Ala165Thr) in MUTYH gene is a missense change that involves a conserved nucleotide and 4/4 in silico tools predict deleterious outcome. The variant of interest is located within the HhH-GPD domain, however, the functional impact of this missense change is yet to be studied. The variant is present in the large control population dataset of ExAC at a frequency 0.00005 (6/121048 chrs tested), which does not exceed the estimated maximal expected allele frequency of a pathogenic variant in this gene (0.0056). The variant has not, to our knowledge, been reported in affected individuals. In addition, several reputable databases/clinical laboratories cite the variant as VUS. At this time there is not sufficient undeniable evidence to classify this variant with confidence. Taken together, the variant was classified as VUS until more data becomes available.
Counsyl RCV000228243 SCV000792228 uncertain significance MYH-associated polyposis 2017-06-13 criteria provided, single submitter clinical testing
GeneKor MSA RCV000165474 SCV000822074 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-01 criteria provided, single submitter clinical testing

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