ClinVar Miner

Submissions for variant NM_001048174.2(MUTYH):c.1347G>C (p.Thr449=) (rs74318065)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000162570 SCV000212986 benign Hereditary cancer-predisposing syndrome 2014-12-17 criteria provided, single submitter clinical testing General population or sub-population frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance;Other data supporting benign classification
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000174706 SCV000226060 benign not specified 2014-08-21 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000174706 SCV000539813 benign not specified 2016-03-29 criteria provided, single submitter clinical testing Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Silent, high frequency
Invitae RCV001083142 SCV000557584 benign MYH-associated polyposis 2020-12-06 criteria provided, single submitter clinical testing
Color Health, Inc RCV000162570 SCV000685576 benign Hereditary cancer-predisposing syndrome 2016-03-21 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000174706 SCV000806343 benign not specified 2016-03-21 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000174706 SCV000889520 benign not specified 2020-08-31 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001282588 SCV001159237 benign none provided 2019-09-29 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000759880 SCV001248076 likely benign not provided 2020-01-01 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001083142 SCV001253573 likely benign MYH-associated polyposis 2018-02-09 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. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001353747 SCV000592717 uncertain significance Carcinoma of colon no assertion criteria provided clinical testing The p.Thr477Thr (c.1431G>C ) variant (alias 1389G>C) has been previously reported in the literature in 14/332 proband chromosomes (frequency 0.048) in individuals affected with either adenomatous polyposis, gastric cancer or colorectal cancer, however controls were not included in these studies (Peterlongo 2006, Tao 2004, Yanaru-Fujisawa 2008). This variant has also been identified in the HGMD and LOVD databases, however it is not expected to have clinical significance because it does not alter an amino acid residue, is not located near a splice junction, and has been reported in dbSNP (ID#:rs74318065), by the 1000 genomes project (frequency 0.016), and ESP project (frequency 0.004). However, there is some conflicting information in the literature. In one study the variant c.1431G > C was found to be in complete linkage disequilibrium with two other MUTYH variants, –280G > A and c.36+11C>T (alias IVS1+11C>T). A statistically significant association was demonstrated between one of these variants, c.36+11C>T and increased CRC risk (Tao 2008). This indicates that individuals with the MUTYH – 280A/c.36+11T/c.1431C genotypes may be susceptible to CRC (Tao 2008). However, replication in additional cohorts and additional functional evidence would be required to validate this finding. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time. Therefore, this variant is classified as a variant of unknown significance (VUS).
True Health Diagnostics RCV000162570 SCV000788064 likely benign Hereditary cancer-predisposing syndrome 2017-06-21 no assertion criteria provided clinical testing

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