ClinVar Miner

Submissions for variant NM_001048171.1(MUTYH):c.1363G>A (p.Val455Ile) (rs779701238)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000166365 SCV000217154 uncertain significance Hereditary cancer-predisposing syndrome 2019-05-15 criteria provided, single submitter clinical testing The p.V469I variant (also known as c.1405G>A), located in coding exon 14 of the MUTYH gene, results from a G to A substitution at nucleotide position 1405. The valine at codon 469 is replaced by isoleucine, an amino acid with highly similar 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. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV000197060 SCV000254701 uncertain significance MYH-associated polyposis 2020-09-24 criteria provided, single submitter clinical testing This sequence change replaces valine with isoleucine at codon 469 of the MUTYH protein (p.Val469Ile). The valine residue is weakly conserved and there is a small physicochemical difference between valine and isoleucine. This variant is present in population databases (rs779701238, ExAC 0.001%). This variant has not been reported in the literature in individuals with MUTYH-related disease. ClinVar contains an entry for this variant (Variation ID: 186723). 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 tolerated, 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.
GeneDx RCV000484811 SCV000567080 uncertain significance not provided 2016-05-27 criteria provided, single submitter clinical testing This variant is denoted MUTYH c.1405G>A at the cDNA level, p.Val469Ile (V469I) at the protein level, and results in the change of a Valine to an Isoleucine (GTA>ATA). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. MUTYH Val469Ile was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Valine and Isoleucine share similar properties, this is considered a conservative amino acid substitution. MUTYH Val469Ile occurs at a position that is not conserved and is located in the Nudix domain (Ruggieri 2013, UniProt). In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available information, it is unclear whether MUTYH Val469Ile is pathogenic or benign. We consider it to be a variant of uncertain significance. Of note, MUTYH-Associated Polyposis (MAP) is a recessive condition associated with two pathogenic variants on opposite chromosomes in MUTYH.
Color Health, Inc RCV000166365 SCV000685572 uncertain significance Hereditary cancer-predisposing syndrome 2020-11-03 criteria provided, single submitter clinical testing This missense variant replaces valine with isoleucine at codon 469 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 4/251492 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.
Counsyl RCV000197060 SCV000790221 uncertain significance MYH-associated polyposis 2017-03-08 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.