ClinVar Miner

Submissions for variant NM_000249.4(MLH1):c.1959G>T (p.Leu653=) (rs1800146)

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Total submissions: 23
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000030219 SCV000106434 no known pathogenicity Lynch syndrome 2013-09-05 reviewed by expert panel research Synonymous substitution with no splicing aberration, >3 MSS CRC tumours, segregation LR <0.01 & MAF 0.01-1%
Invitae RCV000524259 SCV000153861 benign Hereditary nonpolyposis colorectal neoplasms 2020-12-07 criteria provided, single submitter clinical testing
GeneDx RCV000153507 SCV000170299 benign not specified 2013-10-25 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.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000153507 SCV000203027 benign not specified 2014-03-26 criteria provided, single submitter clinical testing
Ambry Genetics RCV000126778 SCV000212672 benign Hereditary cancer-predisposing syndrome 2016-10-25 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.
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics,Children's Hospital of Philadelphia RCV000030219 SCV000257650 benign Lynch syndrome 2015-07-22 criteria provided, single submitter clinical testing
Color Health, Inc RCV000126778 SCV000292111 benign Hereditary cancer-predisposing syndrome 2014-11-26 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000153507 SCV000303147 benign not specified criteria provided, single submitter clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000610651 SCV000744682 benign Lynch syndrome II 2015-09-21 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center RCV000610651 SCV000745681 benign Lynch syndrome II 2015-05-08 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000153507 SCV001156602 benign not specified 2018-07-31 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000610651 SCV001305813 uncertain significance Lynch syndrome II 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). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled 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 RCV001257244 SCV001433776 benign not provided 2017-05-18 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000030219 SCV000052886 benign Lynch syndrome 2013-04-18 no assertion criteria provided clinical testing
Pathway Genomics RCV000144610 SCV000189937 benign Lynch syndrome I 2014-07-24 no assertion criteria provided clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000153507 SCV000257075 benign not specified no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001353935 SCV000592429 benign Carcinoma of colon no assertion criteria provided clinical testing The p.Leu653Leu variant is not expected to have clinical significance because it does not alter an amino acid residue and is not located near a splice junction. It is listed in dbSNP database as coming from a "clinical source" (ID#: rs1801426) with an average heterozygosity of 0.022+/-0.102, increasing the likelihood that this is a low frequency benign variant. The variant has been previously reported in the literature in 9 publications in 20 of 2288 proband chromosomes (frequency of 0.013) with colon cancer, breast cancer, prostate cancer and endometrial cancer, and was also identified in 39 of 2846 control chromosomes (frequency of 0.014), increasing the likelihood that this is a benign variant (Auclaire_16395668_2006, Buerstedde_ 8592341_1995, Christensen_18547406_2008, Fredriksson_16963262_2006, Kamory_14688830_2003, Lamberti_17095871_2006, Liu_9611074_1998, Scott_11112663_2001). In one report this variant was identified at a higher frequency in controls than in cases (Christensen_18547406_2008). In summary, based on the information above, this variant is classified as Benign.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000610651 SCV000734272 likely benign Lynch syndrome II no assertion criteria provided clinical testing
True Health Diagnostics RCV000126778 SCV000788020 likely benign Hereditary cancer-predisposing syndrome 2017-12-08 no assertion criteria provided clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV000153507 SCV001798253 benign not specified no assertion criteria provided clinical testing
Clinical Genetics Laboratory, Department of Pathology,Netherlands Cancer Institute RCV000153507 SCV001905719 benign not specified no assertion criteria provided clinical testing
Clinical Genetics,Academic Medical Center RCV000153507 SCV001920947 benign not specified no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV000153507 SCV001953573 benign not specified no assertion criteria provided clinical testing

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