ClinVar Miner

Submissions for variant NM_001128425.1(MUTYH):c.1513T>G (p.Cys505Gly) (rs876659488)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000229418 SCV000285935 uncertain significance MYH-associated polyposis 2020-11-02 criteria provided, single submitter clinical testing This sequence change replaces cysteine with glycine at codon 505 of the MUTYH protein (p.Cys505Gly). The cysteine residue is moderately conserved and there is a large physicochemical difference between cysteine and glycine. 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 conditions. ClinVar contains an entry for this variant (Variation ID: 238339). 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 glycine 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 RCV000566512 SCV000666475 uncertain significance Hereditary cancer-predisposing syndrome 2018-03-24 criteria provided, single submitter clinical testing The p.C505G variant (also known as c.1513T>G), located in coding exon 15 of the MUTYH gene, results from a T to G substitution at nucleotide position 1513. The cysteine at codon 505 is replaced by glycine, an amino acid with highly dissimilar properties. This amino acid position is not well 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000587590 SCV000697682 uncertain significance not provided 2016-07-15 criteria provided, single submitter clinical testing Variant summary: The MUTYH c.1513T>G (p.Cys505Gly) variant causes a missense change involving a non-conserved nucleotide with 3/4 in silico tools (SNPs&GO not captured due to low reliability index) predicting a "benign" outcome, although these predictions have yet to be functionally assessed. The variant of interest was not observed in controls (ExAC, 1000 Gs or ESP), nor has it been, to our knowledge, reported in affected individuals via publications. However, a clinical laboratory does cite the variant as "uncertain significance." Therefore, taking all available lines of evidence into consideration, the variant of interest has been classified as a "Variant of Uncertain Significance (VUS)," until additional information is available.
Color Health, Inc RCV000566512 SCV000905261 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-30 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000587590 SCV001134468 uncertain significance not provided 2019-05-03 criteria provided, single submitter clinical testing

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