ClinVar Miner

Submissions for variant NM_001048174.2(MUTYH):c.1057G>T (p.Gly353Trp)

gnomAD frequency: 0.00001  dbSNP: rs587778539
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000198794 SCV000254699 uncertain significance Familial adenomatous polyposis 2 2024-07-13 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with tryptophan, which is neutral and slightly polar, at codon 381 of the MUTYH protein (p.Gly381Trp). This variant is present in population databases (rs587778539, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with MUTYH-related conditions. ClinVar contains an entry for this variant (Variation ID: 134863). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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 Diagnostics, LLC DBA Color Health RCV000580244 SCV000685543 uncertain significance Hereditary cancer-predisposing syndrome 2023-09-01 criteria provided, single submitter clinical testing This missense variant replaces glycine with tryptophan at codon 381 of the MUTYH protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported with a co-occurring pathogenic variant (c.91del p.Ala31PhefsT*27) in an individual affected with colorectal cancer (PMID: 35668106). This variant has been identified in 2/250112 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.
Mendelics RCV000198794 SCV000837755 uncertain significance Familial adenomatous polyposis 2 2018-07-02 criteria provided, single submitter clinical testing
Ambry Genetics RCV000580244 SCV002616206 uncertain significance Hereditary cancer-predisposing syndrome 2023-03-22 criteria provided, single submitter clinical testing The p.G381W variant (also known as c.1141G>T), located in coding exon 12 of the MUTYH gene, results from a G to T substitution at nucleotide position 1141. The glycine at codon 381 is replaced by tryptophan, an amino acid with highly dissimilar properties. This amino acid position is not well 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.
Revvity Omics, Revvity RCV000198794 SCV003817130 uncertain significance Familial adenomatous polyposis 2 2019-12-04 criteria provided, single submitter clinical testing
GeneDx RCV003317093 SCV004021620 uncertain significance not provided 2022-06-10 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 23108399, 24728327)
All of Us Research Program, National Institutes of Health RCV000198794 SCV004838415 uncertain significance Familial adenomatous polyposis 2 2023-06-26 criteria provided, single submitter clinical testing This missense variant replaces glycine with tryptophan at codon 381 of the MUTYH protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported with a co-occurring pathogenic variant in an individual affected with colorectal cancer (PMID: 35668106). This variant has been identified in 2/250112 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.
Baylor Genetics RCV000198794 SCV005056030 uncertain significance Familial adenomatous polyposis 2 2024-03-19 criteria provided, single submitter clinical testing
ITMI RCV000121596 SCV000085792 not provided not specified 2013-09-19 no assertion provided reference population

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