ClinVar Miner

Submissions for variant NM_012222.2(MUTYH):c.1592G>A (p.Arg531Gln) (rs3219497)

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Total submissions: 16
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001079890 SCV000153956 benign MYH-associated polyposis 2020-12-07 criteria provided, single submitter clinical testing
GeneDx RCV000121604 SCV000170418 benign not specified 2013-12-30 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 RCV000132024 SCV000187083 benign Hereditary cancer-predisposing syndrome 2014-11-21 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000121604 SCV000601642 likely benign not specified 2017-04-24 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000121604 SCV000806351 benign not specified 2017-01-17 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000121604 SCV000859946 benign not specified 2018-03-09 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000034674 SCV000889531 benign not provided 2018-05-02 criteria provided, single submitter clinical testing
Color Health, Inc RCV000132024 SCV000910546 benign Hereditary cancer-predisposing syndrome 2015-12-17 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001281785 SCV001156739 benign none provided 2020-03-20 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001079890 SCV001257599 benign MYH-associated polyposis 2018-01-31 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). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000121604 SCV001361125 benign not specified 2019-10-21 criteria provided, single submitter clinical testing Variant summary: MUTYH c.1601G>A (p.Arg534Gln) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0027 in 252838 control chromosomes, predominantly at a frequency of 0.038 within the African or African-American subpopulation in the gnomAD database, including 8 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 8-fold the estimated maximal pathogenioc allele frequency expected for a variant in MUTYH causing MUTYH-associated Polyposis phenotype (0.0046), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. c.1601G>A has been reported in the literature in individuals affected with lung cancer (e.g. Fleischmann_2004) and colorectal adenoma (e.g. Olschwang_2007) without storng evidence for causality. These reports do not provide unequivocal conclusions about association of the variant with MUTYH-associated Polyposis. Co-occurrences with other pathogenic variants have been reported (BRCA1 c.5177_5180delGAAA, MLH1 c.677G>A, PALB2 c.172_175delTTGT; all internal LCA samples), providing supporting evidence for a benign role. Several publications evaluating the variant's impact on protein function report conflicting results (Brinkmeyer_2015, Komine_2015). Six other clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000034674 SCV000043364 no known pathogenicity not provided 2012-07-13 no assertion criteria provided research Converted during submission to Benign.
ITMI RCV000121604 SCV000085801 not provided not specified 2013-09-19 no assertion provided reference population
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001353914 SCV000592723 benign Carcinoma of colon no assertion criteria provided clinical testing #N/A
True Health Diagnostics RCV000132024 SCV000886690 likely benign Hereditary cancer-predisposing syndrome 2018-11-16 no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center RCV000121604 SCV001808289 benign not specified no assertion criteria provided clinical testing

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