ClinVar Miner

Submissions for variant NM_001128425.1(MUTYH):c.1532C>T (p.Ser511Phe) (rs796921537)

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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 RCV000566025 SCV000670176 uncertain significance Hereditary cancer-predisposing syndrome 2019-11-18 criteria provided, single submitter clinical testing The p.S511F variant (also known as c.1532C>T), located in coding exon 16 of the MUTYH gene, results from a C to T substitution at nucleotide position 1532. The serine at codon 511 is replaced by phenylalanine, an amino acid with highly dissimilar properties. This amino acid position is 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.
Color Health, Inc RCV000566025 SCV000685592 uncertain significance Hereditary cancer-predisposing syndrome 2020-09-16 criteria provided, single submitter clinical testing This missense variant replaces serine with phenylalanine at codon 511 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 2/282688 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000589299 SCV000697683 uncertain significance not provided 2016-07-15 criteria provided, single submitter clinical testing Variant summary: The c.1532C>T (p.Ser511Phe) in MUTYH gene is a missense change that involves a mildly conserved nucleotide and 2/5 in silico tools predict benign outcome. The variant of interest is located outside of any known functional domain. The variant is absent from the control population dataset of ExAC and has not, to our knowledge, been reported in affected individuals via published reports or by reputable databases/clinical laboratories. Taking together, the variant was classified as VUS.
Invitae RCV001056140 SCV001220561 uncertain significance MYH-associated polyposis 2020-09-03 criteria provided, single submitter clinical testing This sequence change replaces serine with phenylalanine at codon 511 of the MUTYH protein (p.Ser511Phe). The serine residue is moderately conserved and there is a large physicochemical difference between serine and phenylalanine. 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 conditions. ClinVar contains an entry for this variant (Variation ID: 483928). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Benign; Align-GVGD: Class C0). 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.

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