Submissions for variant NM_000249.4(MLH1):c.1963A>G (p.Ile655Val)

gnomAD frequency: 0.00297  dbSNP: rs55907433

Total submissions: 28

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT)	RCV000075440	SCV000106437	likely benign	Lynch syndrome	2013-09-05	reviewed by expert panel	research	MAF 1% in African population
Invitae	RCV001083015	SCV000166246	benign	Hereditary nonpolyposis colorectal neoplasms	2024-01-31	criteria provided, single submitter	clinical testing
GeneDx	RCV000034543	SCV000170300	benign	not provided	2018-12-03	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 15133479, 18809606, 26332594, 22703879, 24055113, 16995940, 21056691, 21681552, 25637381, 22736432, 22949387, 20981092, 24728327, 12115348, 27153395, 18561205, 18383312, 16341804, 24933000, 17510385, 31784484)
Ambry Genetics	RCV000130675	SCV000185561	benign	Hereditary cancer-predisposing syndrome	2014-11-18	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.
Eurofins Ntd Llc (ga)	RCV000121364	SCV000226564	benign	not specified	2015-05-01	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000121364	SCV000595805	likely benign	not specified	2017-05-30	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000130675	SCV000684785	benign	Hereditary cancer-predisposing syndrome	2015-10-15	criteria provided, single submitter	clinical testing
Center for Human Genetics, Inc, Center for Human Genetics, Inc	RCV000659875	SCV000781762	likely benign	Colorectal cancer, hereditary nonpolyposis, type 2	2016-11-01	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000121364	SCV000805960	benign	not specified	2017-12-01	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000034543	SCV000889394	benign	not provided	2022-06-09	criteria provided, single submitter	clinical testing
Mendelics	RCV000659875	SCV001136430	benign	Colorectal cancer, hereditary nonpolyposis, type 2	2019-05-28	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000659875	SCV001305814	likely benign	Colorectal cancer, hereditary nonpolyposis, type 2	2019-04-23	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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000034543	SCV001433781	likely benign	not provided	2017-10-06	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000130675	SCV002528699	benign	Hereditary cancer-predisposing syndrome	2021-04-27	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000121364	SCV002550461	likely benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002496517	SCV002812017	likely benign	Mismatch repair cancer syndrome 1; Muir-Torré syndrome; Colorectal cancer, hereditary nonpolyposis, type 2	2021-10-11	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000034543	SCV002821176	likely benign	not provided	2024-03-01	criteria provided, single submitter	clinical testing	MLH1: BP4
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000659875	SCV004015872	likely benign	Colorectal cancer, hereditary nonpolyposis, type 2	2023-07-07	criteria provided, single submitter	clinical testing
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.	RCV000130675	SCV004228023	benign	Hereditary cancer-predisposing syndrome	2023-11-14	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV000075440	SCV004843244	benign	Lynch syndrome	2024-02-05	criteria provided, single submitter	clinical testing
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000659875	SCV000043328	benign	Colorectal cancer, hereditary nonpolyposis, type 2	2023-10-03	no assertion criteria provided	research	BA1 based on allele frequency in AFR of 0.008856 in gnomAD.
ITMI	RCV000121364	SCV000085545	not provided	not specified	2013-09-19	no assertion provided	reference population
CSER _CC_NCGL, University of Washington	RCV000148615	SCV000190330	likely benign	Endometrial carcinoma	2014-06-01	no assertion criteria provided	research
Mayo Clinic Laboratories, Mayo Clinic	RCV000121364	SCV000257076	likely benign	not specified		no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000034543	SCV000592430	uncertain significance	not provided		flagged submission	clinical testing
True Health Diagnostics	RCV000130675	SCV000788021	likely benign	Hereditary cancer-predisposing syndrome	2017-10-10	no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000121364	SCV002034149	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000121364	SCV002034431	benign	not specified		no assertion criteria provided	clinical testing