ClinVar Miner

Submissions for variant NM_001048171.1(MUTYH):c.924C>G (p.Ser308Arg) (rs138833473)

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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 RCV000130715 SCV000185602 uncertain significance Hereditary cancer-predisposing syndrome 2019-03-11 criteria provided, single submitter clinical testing The p.S322R variant (also known as c.966C>G), located in coding exon 11 of the MUTYH gene, results from a C to G substitution at nucleotide position 966. The serine at codon 322 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species, and arginine is the reference amino acid in other 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 RCV000410968 SCV000487347 uncertain significance MYH-associated polyposis 2016-04-13 criteria provided, single submitter clinical testing
Invitae RCV000410968 SCV000761965 uncertain significance MYH-associated polyposis 2019-12-23 criteria provided, single submitter clinical testing This sequence change replaces serine with arginine at codon 322 of the MUTYH protein (p.Ser322Arg). The serine residue is weakly conserved and there is a moderate physicochemical difference between serine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with MUTYH-related disease. ClinVar contains an entry for this variant (Variation ID: 141970). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The arginine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. 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 RCV000130715 SCV000903811 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-30 criteria provided, single submitter clinical testing
GeneDx RCV001564902 SCV001788143 uncertain significance not provided 2019-09-25 no assertion criteria provided clinical testing Not observed at a significant frequency in large population cohorts (Lek 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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