ClinVar Miner

Submissions for variant NM_001048171.1(MUTYH):c.995C>G (p.Ser332Trp) (rs587778538)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000165499 SCV000216230 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-07 criteria provided, single submitter clinical testing ​<span style="background-color:initial">The p.S346W<span style="background-color:initial"> variant (also known as c.1037C>G), located in coding exon 12 of the MUTYH<span style="background-color:initial"> gene, results from a C to G substitution at nucleotide position 1037. The serine at codon 346 is replaced by tryptophan, an amino acid with highly dissimilar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis.<span style="background-color:initial"> Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV000203957 SCV000261495 uncertain significance MYH-associated polyposis 2020-09-10 criteria provided, single submitter clinical testing This sequence change replaces serine with tryptophan at codon 346 of the MUTYH protein (p.Ser346Trp). The serine residue is moderately conserved and there is a large physicochemical difference between serine and tryptophan. This variant is present in population databases (rs587778538, ExAC 0.005%). This variant has been observed in an individual affected with breast cancer (PMID: 30564557). ClinVar contains an entry for this variant (Variation ID: 185982). 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: Possibly Damaging; Align-GVGD: Class C1). 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. 5
Counsyl RCV000203957 SCV000792412 uncertain significance MYH-associated polyposis 2017-06-27 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759877 SCV000889516 uncertain significance not provided 2018-06-27 criteria provided, single submitter clinical testing
Color Health, Inc RCV000165499 SCV001356409 uncertain significance Hereditary cancer-predisposing syndrome 2020-10-27 criteria provided, single submitter clinical testing This missense variant replaces serine with tryptophan at codon 346 of the MUTYH protein. Computational prediction tool 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 been reported in an individual affected with male breast cancer (PMID: 30564557). This variant has been identified in 6/241834 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.
GeneDx RCV000759877 SCV001778064 uncertain significance not provided 2018-10-17 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function

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