ClinVar Miner

Submissions for variant NM_001048171.1(MUTYH):c.529C>T (p.Arg177Trp) (rs761101420)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000165580 SCV000216314 uncertain significance Hereditary cancer-predisposing syndrome 2020-09-30 criteria provided, single submitter clinical testing The p.R191W variant (also known as c.571C>T), located in coding exon 7 of the MUTYH gene, results from a C to T substitution at nucleotide position 571. The arginine at codon 191 is replaced by tryptophan, an amino acid with dissimilar properties. This variant was identified in a cohort of 882 Chinese individuals who underwent multi-gene panel testing for HBOC risk assessment (Shao D et al. Cancer Sci., 2020 Feb;111:647-657). 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.
Invitae RCV000204489 SCV000262259 uncertain significance MYH-associated polyposis 2020-10-12 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 191 of the MUTYH protein (p.Arg191Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs761101420, ExAC 0.01%). This variant has been reported in an individual affected with colorectal cancer (PMID: 18294051). This variant is also known as p.Arg177Trp in the literature. ClinVar contains an entry for this variant (Variation ID: 186056). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies. 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 Health, Inc RCV000165580 SCV000685644 uncertain significance Hereditary cancer-predisposing syndrome 2020-09-30 criteria provided, single submitter clinical testing This missense variant replaces arginine with tryptophan at codon 191 of the MUTYH protein. This variant is also known as NM_001048171.1:c.529C>T (p.Arg177Trp) in the literature. 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 in an individual affected with colorectal cancer (PMID: 18294051). This variant has been identified in 3/251480 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.
Counsyl RCV000204489 SCV000797302 uncertain significance MYH-associated polyposis 2018-01-22 criteria provided, single submitter clinical testing
GenomeConnect - Invitae Patient Insights Network RCV000204489 SCV001749674 not provided MYH-associated polyposis no assertion provided phenotyping only Variant interpreted as Uncertain significance and reported on 06-18-2018 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.

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