ClinVar Miner

Submissions for variant NM_012222.2(MUTYH):c.64G>A (p.Val22Met) (rs3219484)

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Total submissions: 15
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000079503 SCV000111385 benign not specified 2012-12-05 criteria provided, single submitter clinical testing
Invitae RCV000119118 SCV000153831 benign MYH-associated polyposis 2020-12-08 criteria provided, single submitter clinical testing
Ambry Genetics RCV000129820 SCV000184634 benign Hereditary cancer-predisposing syndrome 2014-11-18 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.
PreventionGenetics,PreventionGenetics RCV000079503 SCV000306739 benign not specified criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000119118 SCV000357908 benign MYH-associated polyposis 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Color Health, Inc RCV000129820 SCV000537357 benign Hereditary cancer-predisposing syndrome 2015-03-27 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001283415 SCV000604309 benign none provided 2020-08-07 criteria provided, single submitter clinical testing
Institute of Human Genetics, University of Leipzig Medical Center RCV001262768 SCV001440758 benign Breast carcinoma 2019-01-01 criteria provided, single submitter clinical testing
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000034677 SCV000043381 no known pathogenicity not provided 2012-07-13 no assertion criteria provided research Converted during submission to Benign.
ITMI RCV000079503 SCV000085803 not provided not specified 2013-09-19 no assertion provided reference population
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001353454 SCV000592674 benign Carcinoma of colon no assertion criteria provided clinical testing The p.Val22Met variant has been previously reported in the literature in 234 of 7042 (frequency of 0.033) probands with FAP, colorectal cancer, prostate cancer, endometrial cancer and lung cancer, and was also identified in 253 of 6558 (frequency of 0.039) controls increasing the likelihood that this is a low frequency benign variant (Agalliu_2010, Alhopuro_2005, Ali_2008, Al-Tassan_2002, Ashton_2009, Croitoru_2004, Gorgens_2006, Isidro_2004, Kambara_2004, Shimura_2001, Shin_2007). Functional assays of the p.Val22Met variant reveal it to be as active as the WT with full glycosylase activity. This variant is not expected to have clinical significance because it is reported in dbSNP as a common polymorphism (dbSNP#: rs3219484), but no frequency informationw as provided. This residue is not highly conserved in mammals and computational analyses (________, SIFT, AlignGVGD) do not suggest a high likelihood of impact to the protein. However, this information is not predictive enough to rule out pathogenicity. In summary, based on the above information, this variant is classified as benign.
Mayo Clinic Laboratories, Mayo Clinic RCV000079503 SCV000691953 benign not specified no assertion criteria provided clinical testing
True Health Diagnostics RCV000129820 SCV000788072 benign Hereditary cancer-predisposing syndrome 2018-02-20 no assertion criteria provided clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000079503 SCV001739872 benign not specified no assertion criteria provided clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV000079503 SCV001797727 benign not specified no assertion criteria provided clinical testing

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