ClinVar Miner

Submissions for variant NM_001048174.2(MUTYH):c.827G>A (p.Ser276Asn)

dbSNP: rs1553127574
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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 RCV000573304 SCV000670123 uncertain significance Hereditary cancer-predisposing syndrome 2022-02-01 criteria provided, single submitter clinical testing The p.S304N variant (also known as c.911G>A), located in coding exon 10 of the MUTYH gene, results from a G to A substitution at nucleotide position 911. The serine at codon 304 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is not 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.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000613114 SCV000731348 uncertain significance not specified 2017-01-17 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The p.Ser304Asn var iant in MUTYH has not been reported in individuals with MUTYH-associated polypos is and was absent from large population studies. Serine (Ser) at position 304 is poorly conserved in evolution and 3 mammals have the variant amino acid (Asn) a t this position, suggesting that this change may be tolerated. Additional compu tational prediction tools suggest that the p.Ser304Asn variant may not impact th e protein, though this information is not predictive enough to rule out pathogen icity. In summary, while the clinical significance of the p.Ser304Asn variant is uncertain, the lack of evolutionary conservation suggests that it is more likel y to be benign.
Color Diagnostics, LLC DBA Color Health RCV000573304 SCV000911217 uncertain significance Hereditary cancer-predisposing syndrome 2023-03-16 criteria provided, single submitter clinical testing This missense variant replaces serine with asparagine at codon 304 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 MUTYH-related disorders in the literature. This variant has not been identified 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.
Invitae RCV000798937 SCV000938581 uncertain significance Familial adenomatous polyposis 2 2024-01-04 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 304 of the MUTYH protein (p.Ser304Asn). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MUTYH-related conditions. ClinVar contains an entry for this variant (Variation ID: 483890). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The asparagine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
GeneDx RCV001755945 SCV001994932 uncertain significance not provided 2019-10-21 criteria provided, single submitter clinical testing Not observed 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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