Submissions for variant NM_000249.4(MLH1):c.1853A>C (p.Lys618Thr)

dbSNP: rs63750449

Total submissions: 22

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT)	RCV000075384	SCV000106379	no known pathogenicity	Lynch syndrome	2013-09-05	reviewed by expert panel	research	Multifactorial likelihood analysis posterior probability <0.001
Ambry Genetics	RCV000132375	SCV000187465	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)	RCV000174993	SCV000226409	likely benign	not specified	2014-09-24	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000132375	SCV000537392	benign	Hereditary cancer-predisposing syndrome	2022-01-01	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000174993	SCV000539634	benign	not specified	2020-08-10	criteria provided, single submitter	clinical testing	The p.Lys618Thr variant in MLH1 is classified as benign because it has been identified in 0.57% (735/129116, 2 homozygotes) chromosomes by gnomAD (http://gnomad.broadinstitute.org) and is a common haplotype with c.1852A>G. ACMG/AMP Criteria applied: BA1.
Genetic Services Laboratory, University of Chicago	RCV000174993	SCV000595804	likely benign	not specified	2017-04-03	criteria provided, single submitter	clinical testing
Invitae	RCV001080445	SCV000751221	benign	Hereditary nonpolyposis colorectal neoplasms	2024-01-18	criteria provided, single submitter	clinical testing
Mendelics	RCV000615824	SCV001136426	benign	Colorectal cancer, hereditary nonpolyposis, type 2	2019-05-28	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000615824	SCV001305811	uncertain significance	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 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.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000174993	SCV001470327	benign	not specified	2019-11-12	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000114853	SCV001748066	likely benign	not provided	2023-08-01	criteria provided, single submitter	clinical testing	MLH1: PP3, BS2
Sema4, Sema4	RCV000132375	SCV002528688	benign	Hereditary cancer-predisposing syndrome	2020-05-10	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000174993	SCV002550417	benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002498362	SCV002809640	likely benign	Mismatch repair cancer syndrome 1; Muir-Torré syndrome; Colorectal cancer, hereditary nonpolyposis, type 2	2022-04-21	criteria provided, single submitter	clinical testing
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.	RCV000132375	SCV002819230	benign	Hereditary cancer-predisposing syndrome	2022-11-22	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003149735	SCV003838214	likely benign	Breast and/or ovarian cancer	2023-06-22	criteria provided, single submitter	clinical testing
Harris Lab, University of Minnesota	RCV000114853	SCV000148748	not provided	not provided		no assertion provided	not provided
Pathway Genomics	RCV000144601	SCV000189928	likely benign	Lynch syndrome 1	2014-07-24	no assertion criteria provided	clinical testing
CSER _CC_NCGL, University of Washington	RCV000148619	SCV000190334	uncertain significance	Colorectal cancer, non-polyposis	2014-06-01	no assertion criteria provided	research
Mayo Clinic Laboratories, Mayo Clinic	RCV000174993	SCV000257071	uncertain significance	not specified		no assertion criteria provided	research
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000114853	SCV000592425	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000174993	SCV001970435	benign	not specified		no assertion criteria provided	clinical testing