ClinVar Miner

Submissions for variant NM_001048171.1(MUTYH):c.158-33G>T (rs587781374)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129189 SCV000183927 uncertain significance Hereditary cancer-predisposing syndrome 2020-07-29 criteria provided, single submitter clinical testing The p.G56V variant (also known as c.167G>T), located in coding exon 3 of the MUTYH gene, results from a G to T substitution at nucleotide position 167. The glycine at codon 56 is replaced by valine, an amino acid with 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.
Counsyl RCV000409275 SCV000487383 uncertain significance MYH-associated polyposis 2016-10-27 criteria provided, single submitter clinical testing
Invitae RCV000409275 SCV000639300 uncertain significance MYH-associated polyposis 2020-10-27 criteria provided, single submitter clinical testing This sequence change replaces glycine with valine at codon 56 of the MUTYH protein (p.Gly56Val). The glycine residue is weakly conserved and there is a moderate physicochemical difference between glycine and valine. This variant is present in population databases (rs587781374, ExAC 0.002%) but has not been reported in the literature in individuals with a MUTYH-related disease. ClinVar contains an entry for this variant (Variation ID: 140924). 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, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Color Health, Inc RCV000129189 SCV000905866 uncertain significance Hereditary cancer-predisposing syndrome 2021-02-01 criteria provided, single submitter clinical testing This missense variant replaces glycine with valine at codon 56 of the MUTYH protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 2/248342 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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