ClinVar Miner

Submissions for variant NM_001048174.2(MUTYH):c.592A>G (p.Ile198Val)

gnomAD frequency: 0.00001  dbSNP: rs200965879
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000164430 SCV000215069 uncertain significance Hereditary cancer-predisposing syndrome 2022-11-18 criteria provided, single submitter clinical testing The p.I226V variant (also known as c.676A>G), located in coding exon 8 of the MUTYH gene, results from an A to G substitution at nucleotide position 676. The isoleucine at codon 226 is replaced by valine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Color Diagnostics, LLC DBA Color Health RCV000164430 SCV000685655 uncertain significance Hereditary cancer-predisposing syndrome 2022-08-01 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with valine at codon 226 of the MUTYH protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in individuals affected with breast cancer (PMID: 23383274, 33471991). This variant has been identified in 2/282736 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 RCV000669978 SCV000794784 uncertain significance Familial adenomatous polyposis 2 2017-10-17 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000669978 SCV000935687 uncertain significance Familial adenomatous polyposis 2 2024-01-21 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 226 of the MUTYH protein (p.Ile226Val). This variant is present in population databases (rs200965879, gnomAD 0.005%). 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: 185072). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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 RCV001559546 SCV001781792 uncertain significance not provided 2019-09-17 criteria provided, single submitter clinical testing 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
Sema4, Sema4 RCV000164430 SCV002532311 uncertain significance Hereditary cancer-predisposing syndrome 2021-04-29 criteria provided, single submitter curation
All of Us Research Program, National Institutes of Health RCV000669978 SCV004841570 uncertain significance Familial adenomatous polyposis 2 2023-06-28 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with valine at codon 226 of the MUTYH protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in individuals affected with breast cancer (PMID: 23383274, 33471991). This variant has been identified in 2/282736 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.

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.