ClinVar Miner

Submissions for variant NM_000249.4(MLH1):c.1321G>A (p.Ala441Thr) (rs63750365)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 19
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000075170 SCV000106161 no known pathogenicity Lynch syndrome 2013-09-05 reviewed by expert panel research Multifactorial likelihood analysis posterior probability <0.001
GeneDx RCV000202064 SCV000149365 likely benign not specified 2017-12-14 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 RCV000115456 SCV000184608 benign Hereditary cancer-predisposing syndrome 2019-01-17 criteria provided, single submitter clinical testing Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation;Deficient protein function in appropriate functional assay(s);In silico models in agreement (benign);Subpopulation frequency in support of benign classification;Other data supporting benign classification;Co-occurence with mutation in same gene (phase unknown)
Invitae RCV001083668 SCV000219061 benign Hereditary nonpolyposis colorectal neoplasms 2019-12-31 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000202064 SCV000539641 uncertain significance not specified 2017-01-10 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: Two mammals and one non-mammal have a Thr at this position. It has a max MAF of 0.09% in gnomAD. It is reported in 7 papers in HGMD, classified as DM, most comments suggest VUS. It is classified in ClinVar with 3 stars as Benign by InSiGHT (expert panel) and Pathway genomics, and likely benign by GeneDx and Invitae, and as VUS by Mayo and CSER_CC_NCGL.
Genetic Services Laboratory,University of Chicago RCV000202064 SCV000595807 uncertain significance not specified 2017-03-10 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000202064 SCV000601351 uncertain significance not specified 2017-07-03 criteria provided, single submitter clinical testing
Center for Human Genetics, Inc,Center for Human Genetics, Inc RCV000659870 SCV000781755 uncertain significance Lynch syndrome II 2016-11-01 criteria provided, single submitter clinical testing
Counsyl RCV000659870 SCV000786114 likely benign Lynch syndrome II 2018-02-28 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000679266 SCV000805947 likely benign not provided 2017-04-03 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000679266 SCV000884118 benign not provided 2018-02-05 criteria provided, single submitter clinical testing
Color RCV000115456 SCV000902604 benign Hereditary cancer-predisposing syndrome 2015-10-15 criteria provided, single submitter clinical testing
Mendelics RCV000659870 SCV001136408 benign Lynch syndrome II 2019-05-28 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000679266 SCV001153842 likely benign not provided 2019-02-01 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000659870 SCV001308772 uncertain significance Lynch syndrome II 2018-03-29 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.
Pathway Genomics RCV000144611 SCV000189938 benign Lynch syndrome I 2014-07-24 no assertion criteria provided clinical testing
CSER _CC_NCGL, University of Washington RCV000148618 SCV000190333 uncertain significance Colorectal cancer, non-polyposis 2014-06-01 no assertion criteria provided research
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000202064 SCV000257050 uncertain significance not specified no assertion criteria provided research
True Health Diagnostics RCV000115456 SCV000788017 likely benign Hereditary cancer-predisposing syndrome 2017-08-30 no assertion criteria provided clinical testing

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.