ClinVar Miner

Submissions for variant NM_001048171.1(MUTYH):c.1076C>T (p.Ala359Val) (rs35352891)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 13
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000123139 SCV000166441 likely benign MYH-associated polyposis 2019-12-31 criteria provided, single submitter clinical testing
GeneDx RCV000417387 SCV000211422 likely benign not specified 2018-01-20 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Ambry Genetics RCV000160763 SCV000214342 likely benign Hereditary cancer-predisposing syndrome 2018-06-11 criteria provided, single submitter clinical testing Intact protein function observed by in vitro/ex vivo assays;In silico models in agreement (benign) ;Sub-population frequency in support of benign classification (not ava blue, manual h-w);Seen in conjunction with two deleterious mutations confirmed in trans in symptomatic individuals
Counsyl RCV000123139 SCV000487369 likely benign MYH-associated polyposis 2016-07-18 criteria provided, single submitter clinical testing
Institute for Biomarker Research,Medical Diagnostic Laboratories, L.L.C. RCV000160763 SCV000576449 uncertain significance Hereditary cancer-predisposing syndrome 2017-02-14 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000417387 SCV000592708 likely benign not specified 2014-05-07 criteria provided, single submitter clinical testing
Color RCV000160763 SCV000685541 benign Hereditary cancer-predisposing syndrome 2016-03-21 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000417387 SCV000917803 likely benign not specified 2019-07-18 criteria provided, single submitter clinical testing Variant summary: MUTYH c.1118C>T (p.Ala373Val) results in a non-conservative amino acid change located in the MutY, C-terminal domain (IPR029119) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0004 in 250664 control chromosomes, predominantly at a frequency of 0.0046 within the East Asian subpopulation in the gnomAD database. This frequency is comparable to the estimated maximal expected allele frequency of a pathogenic MUTYH variant (0.0046). In addition, the variant was found in certain East Asian subpopulations with even higher frequencies, e.g. in Koreans (0.0068; gnomAD) and in Japanese (0.0091, including 1 homozygote; HGVD), suggesting that the variant is a benign polymorphism found primarily in populations of East Asian origin. Multiple publications have cited the variant in affected individuals, including one patient presenting with colorectal polyposis, who was homozygous for the variant of interest and also carried the likely pathogenic variant G272E in a homozygous state (Yanaru-Fujisawa_2008). At least two publications reported experimental evidence evaluating an impact on protein function, and demonstrated no damaging effect for this variant (Goto_2010, Yanaru-Fujisawa_2008). Seven other submitters have provided clinical-significance assessments for this variant in ClinVar after 2014 without evidence for independent evaluation, and classified the variant with conflicting assessments: pathogenic (1x), VUS (1x), likely benign (4x) or benign (1x). Based on the evidence outlined above, the variant was classified as likely benign.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000034668 SCV001134465 likely benign not provided 2019-01-25 criteria provided, single submitter clinical testing
Mendelics RCV000123139 SCV001135253 likely benign MYH-associated polyposis 2019-05-28 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000123139 SCV001255468 uncertain significance MYH-associated polyposis 2018-10-26 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000034668 SCV000043371 variant of unknown significance not provided 2012-07-13 no assertion criteria provided research Converted during submission to Uncertain significance.
GeneReviews RCV000123139 SCV000246165 pathogenic MYH-associated polyposis 2019-10-08 no assertion criteria provided literature only

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.