ClinVar Miner

Submissions for variant NM_001048174.2(MUTYH):c.228C>T (p.Tyr76=) (rs121908380)

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Total submissions: 16
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000119223 SCV000153967 benign MYH-associated polyposis 2020-12-08 criteria provided, single submitter clinical testing
GeneDx RCV000177119 SCV000170421 benign not specified 2013-11-05 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 RCV000126890 SCV000212844 likely benign Hereditary cancer-predisposing syndrome 2014-06-19 criteria provided, single submitter clinical testing This alteration is classified as likely 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.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000177119 SCV000228946 benign not specified 2015-03-27 criteria provided, single submitter clinical testing
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics,Children's Hospital of Philadelphia RCV000119223 SCV000297027 benign MYH-associated polyposis 2015-12-03 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000177119 SCV000539814 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: ExAC: 0.5% Finnish chromosomes; ClinVar: 4 labs classify as LB/B
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000513902 SCV000609577 likely benign not provided 2017-08-22 criteria provided, single submitter clinical testing
Color Health, Inc RCV000126890 SCV000685610 benign Hereditary cancer-predisposing syndrome 2016-05-03 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000513902 SCV000697690 benign not provided 2016-06-06 criteria provided, single submitter clinical testing Variant summary: The MUTYH c.312C>T (p.Tyr104Tyr) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a damaging outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may affect multiple ESE sites. However, these predictions have yet to be confirmed by functional studies. This variant was found in 161/124730 control chromosomes at a frequency of 0.0012908, which does not exceed the estimated maximal expected allele frequency of a pathogenic MUTYH variant (0.0055902). This variant has been reported in numerous patients with various types of cancer, however, without enough evidence suggesting pathogenicity. In one internal sample (91 y.o.), co-occurrence of this variant and BRIP1 c.484C>T (classified as likely pathogenic by LCA) was found, suggesting the variant of interest is unlikely to be pathogenic. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign. Taken together, this variant is classified as benign.
PreventionGenetics,PreventionGenetics RCV000513902 SCV000806353 likely benign not provided 2017-07-14 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000513902 SCV000888312 likely benign not provided 2020-07-24 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000513902 SCV001147273 likely benign not provided 2018-05-01 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000119223 SCV001257410 uncertain significance MYH-associated polyposis 2017-04-27 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.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001286507 SCV001473093 likely benign none provided 2020-02-16 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001353596 SCV000592678 likely benign Carcinoma of colon no assertion criteria provided clinical testing The MUTYH p.Tyr104= variant was identified in 6 of 8036 proband chromosomes (frequency: 0.001) from individuals or families with colorectal cancer, breast cancer, or adenomatous polyposis and was not identified in 3332 control chromosomes from healthy individuals (Out 2012, Aretz 2006, Alhopuro 2005, McVeigh 2016, Niessen 2006, Olschwang 2007). The variant was also identified in dbSNP (ID: rs121908380) as “With Pathogenic, other allele”, ClinVar (classified as benign by Invitae, GeneDx, Color Genomics and 4 clinical laboratories; as likely benign by Ambry Genetics and 3 clinical laboratories), Clinvitae, and COGR database. The variant was not identified in Cosmic, or UMD-LSDB databases. The variant was identified in control databases in 417 of 277196 chromosomes (1 homozygous) at a frequency of 0.002 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 13 of 24020 chromosomes (freq: 0.001), Other in 16 of 6464 chromosomes (freq: 0.002), Latino in 50 of 34420 chromosomes (freq: 0.001), European in 213 of 126700 chromosomes (freq: 0.002), East Asian in 1 of 18870 chromosomes (freq: 0.0001), Finnish in 123 of 25788 chromosomes (freq: 0.01), and South Asian in 1 of 30782 chromosomes (freq: 0.00003); it was not observed in the Ashkenazi Jewish populations. The p.Tyr104= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.
True Health Diagnostics RCV000126890 SCV000788068 likely benign Hereditary cancer-predisposing syndrome 2017-11-17 no assertion criteria provided clinical testing

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