Submissions for variant NM_000249.4(MLH1):c.1852A>G (p.Lys618Glu)

gnomAD frequency: 0.00399  dbSNP: rs35001569

Total submissions: 19

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000132423	SCV000187516	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: 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)	RCV000174992	SCV000226408	likely benign	not specified	2014-09-24	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000174992	SCV000539633	likely benign	not specified	2016-03-28	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: 1 report in HGMD; ExAC: 0.5% (358/66740) European chromosomes
Invitae	RCV001083570	SCV000555963	benign	Hereditary nonpolyposis colorectal neoplasms	2024-01-30	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000114852	SCV000575343	likely benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing	MLH1: PM5, BS2
Genetic Services Laboratory, University of Chicago	RCV000174992	SCV000595803	likely benign	not specified	2017-04-03	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000132423	SCV000689843	likely benign	Hereditary cancer-predisposing syndrome	2015-01-02	criteria provided, single submitter	clinical testing
Counsyl	RCV000663286	SCV000786528	likely benign	Colorectal cancer, hereditary nonpolyposis, type 2	2018-05-23	criteria provided, single submitter	clinical testing
Mendelics	RCV000075380	SCV000838025	likely benign	Lynch syndrome	2018-07-02	criteria provided, single submitter	clinical testing
Mendelics	RCV000663286	SCV001136425	likely benign	Colorectal cancer, hereditary nonpolyposis, type 2	2019-05-28	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000663286	SCV001305810	likely benign	Colorectal cancer, hereditary nonpolyposis, type 2	2019-06-10	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 allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Sema4, Sema4	RCV000132423	SCV002528687	benign	Hereditary cancer-predisposing syndrome	2020-05-10	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000174992	SCV002550866	benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.	RCV000132423	SCV002819229	benign	Hereditary cancer-predisposing syndrome	2022-11-22	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003149734	SCV003838870	likely benign	Breast and/or ovarian cancer	2023-06-22	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV000663286	SCV004018161	uncertain significance	Colorectal cancer, hereditary nonpolyposis, type 2	2023-03-15	criteria provided, single submitter	clinical testing	This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk.
Harris Lab, University of Minnesota	RCV000114852	SCV000148747	not provided	not provided		no assertion provided	not provided
Mayo Clinic Laboratories, Mayo Clinic	RCV000174992	SCV000257070	uncertain significance	not specified		no assertion criteria provided	research
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000114852	SCV001553065	uncertain significance	not provided		no assertion criteria provided	clinical testing