ClinVar Miner

Submissions for variant NM_001128425.1(MUTYH):c.161G>A (p.Cys54Tyr) (rs560905645)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000204226 SCV000259584 uncertain significance MYH-associated polyposis 2020-10-07 criteria provided, single submitter clinical testing This sequence change replaces cysteine with tyrosine at codon 54 of the MUTYH protein (p.Cys54Tyr). The cysteine residue is weakly conserved and there is a large physicochemical difference between cysteine and tyrosine. This variant is present in population databases (rs560905645, 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: 219610). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: Tolerated; PolyPhen-2: Benign; Align-GVGD: Class C0. The tyrosine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. 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.
Ambry Genetics RCV000220830 SCV000275074 likely benign Hereditary cancer-predisposing syndrome 2018-12-10 criteria provided, single submitter clinical testing Other strong data
Color Health, Inc RCV000220830 SCV000911456 likely benign Hereditary cancer-predisposing syndrome 2017-02-03 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000781623 SCV000919802 uncertain significance not specified 2018-09-14 criteria provided, single submitter clinical testing Variant summary: MUTYH c.161G>A (p.Cys54Tyr) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 242220 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.161G>A in individuals affected with MUTYH-associated Polyposis and no experimental evidence demonstrating its impact on protein function have been reported. Two ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant once as uncertain significance and once as likely benign. Based on the evidence outlined above, the variant was classified as uncertain significance.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000985858 SCV001134473 uncertain significance not provided 2020-07-16 criteria provided, single submitter clinical testing
Mendelics RCV000204226 SCV001135266 likely benign MYH-associated polyposis 2019-05-28 criteria provided, single submitter clinical testing
GeneDx RCV000985858 SCV001771190 uncertain significance not provided 2021-04-21 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function

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