Submissions for variant NM_000249.4(MLH1):c.2146G>A (p.Val716Met)

gnomAD frequency: 0.00143  dbSNP: rs35831931

Total submissions: 28

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT)	RCV000075554	SCV000106550	no known pathogenicity	Lynch syndrome	2013-09-05	reviewed by expert panel	research	Multifactorial likelihood analysis posterior probability <0.001
Eurofins Ntd Llc (ga)	RCV000121366	SCV000110265	likely benign	not specified	2013-01-02	criteria provided, single submitter	clinical testing
GeneDx	RCV000121366	SCV000149381	benign	not specified	2017-07-21	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.
Invitae	RCV001082159	SCV000153862	benign	Hereditary nonpolyposis colorectal neoplasms	2024-02-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000115472	SCV000184334	benign	Hereditary cancer-predisposing syndrome	2014-08-29	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, 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.
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000121366	SCV000592441	benign	not specified	2016-08-12	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000115472	SCV000684801	benign	Hereditary cancer-predisposing syndrome	2014-12-11	criteria provided, single submitter	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000600229	SCV000744683	benign	Colorectal cancer, hereditary nonpolyposis, type 2	2015-09-21	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000034545	SCV000805965	likely benign	not provided	2017-10-03	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000034545	SCV000892682	benign	not provided	2024-04-01	criteria provided, single submitter	clinical testing	MLH1: BS3:Supporting, BS1, BS2
Mendelics	RCV000600229	SCV001136438	likely benign	Colorectal cancer, hereditary nonpolyposis, type 2	2019-05-28	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000600229	SCV001307916	benign	Colorectal cancer, hereditary nonpolyposis, type 2	2019-02-11	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 rule this variant out of causing disease. Therefore, this variant is classified as benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000121366	SCV001433782	benign	not specified	2017-07-03	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001798063	SCV002042075	likely benign	Breast and/or ovarian cancer	2022-12-16	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000121366	SCV002071029	benign	not specified	2018-07-18	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000115472	SCV002528720	benign	Hereditary cancer-predisposing syndrome	2020-07-02	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000121366	SCV002550510	benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.	RCV000115472	SCV004014969	benign	Hereditary cancer-predisposing syndrome	2023-01-24	criteria provided, single submitter	clinical testing
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000600229	SCV000043330	benign	Colorectal cancer, hereditary nonpolyposis, type 2	2023-10-03	no assertion criteria provided	research	BA1 based on allele frequency in NFE of 0.00203 in gnomAD.
ITMI	RCV000121366	SCV000085548	not provided	not specified	2013-09-19	no assertion provided	reference population
Mayo Clinic Laboratories, Mayo Clinic	RCV000121366	SCV000691867	benign	not specified		no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000600229	SCV000734273	likely benign	Colorectal cancer, hereditary nonpolyposis, type 2		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000600229	SCV000745682	benign	Colorectal cancer, hereditary nonpolyposis, type 2	2016-10-21	no assertion criteria provided	clinical testing
Center of Medical Genetics and Primary Health Care	RCV001269371	SCV001448727	benign	Malignant tumor of breast		no assertion criteria provided	clinical testing
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	RCV000121366	SCV001906126	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000034545	SCV001921662	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000121366	SCV001959081	benign	not specified		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000121366	SCV002036458	benign	not specified		no assertion criteria provided	clinical testing