ClinVar Miner

Submissions for variant NM_001128425.1(MUTYH):c.449C>T (p.Thr150Ile) (rs745507536)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000164386 SCV000215021 uncertain significance Hereditary cancer-predisposing syndrome 2019-11-07 criteria provided, single submitter clinical testing The p.T150I variant (also known as c.449C>T), located in coding exon 5 of the MUTYH gene, results from a C to T substitution at nucleotide position 449. The threonine at codon 150 is replaced by isoleucine, an amino acid with similar 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.
Invitae RCV001039571 SCV001203103 uncertain significance MYH-associated polyposis 2020-10-14 criteria provided, single submitter clinical testing This sequence change replaces threonine with isoleucine at codon 150 of the MUTYH protein (p.Thr150Ile). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and isoleucine. This variant is present in population databases (rs745507536, ExAC 0.001%). This variant has not been reported in the literature in individuals with MUTYH-related conditions. ClinVar contains an entry for this variant (Variation ID: 185033). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Benign; Align-GVGD: Class C1). 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. 5
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001194164 SCV001363476 uncertain significance not specified 2019-09-06 criteria provided, single submitter clinical testing Variant summary: MUTYH c.449C>T (p.Thr150Ile) results in a non-conservative amino acid change located in the HhH-GPD domain (IPR003265) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251478 control chromosomes. 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.449C>T in individuals affected with MUTYH-associated Polyposis and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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