ClinVar Miner

Submissions for variant NM_001128425.1(MUTYH):c.1090C>T (p.Arg364Cys) (rs151316420)

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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 RCV000223437 SCV000274900 uncertain significance Hereditary cancer-predisposing syndrome 2020-05-12 criteria provided, single submitter clinical testing The p.R364C variant (also known as c.1090C>T), located in coding exon 12 of the MUTYH gene, results from a C to T substitution at nucleotide position 1090. The arginine at codon 364 is replaced by cysteine, 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.
Invitae RCV000544801 SCV000639250 uncertain significance MYH-associated polyposis 2020-05-04 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 364 of the MUTYH protein (p.Arg364Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs151316420, ExAC 0.006%). This variant has been reported in an individual in the Leiden Open-source Variation Database (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 156508). 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 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.
Color Health, Inc RCV000223437 SCV000685538 uncertain significance Hereditary cancer-predisposing syndrome 2020-10-12 criteria provided, single submitter clinical testing This missense variant replaces arginine with cysteine at codon 364 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 not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 2/249872 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.
Pathway Genomics RCV000144629 SCV000189956 uncertain significance Carcinoma of colon 2014-07-24 no assertion criteria provided clinical testing

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