Submissions for variant NM_000249.4(MLH1):c.790+10A>G

gnomAD frequency: 0.00188  dbSNP: rs182733777

Total submissions: 23

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT)	RCV000075846	SCV000106860	no known pathogenicity	Lynch syndrome	2013-09-05	reviewed by expert panel	research	Multifactorial likelihood analysis posterior probability <0.001
GeneDx	RCV001703976	SCV000170292	benign	not provided	2018-11-29	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 22949379, 25985138, 21239990, 18561205, 26332594, 25871441, 26247049, 18547406, 14688830)
Ambry Genetics	RCV000129433	SCV000184203	benign	Hereditary cancer-predisposing syndrome	2015-09-20	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.
Invitae	RCV000524315	SCV000252651	benign	Hereditary nonpolyposis colorectal neoplasms	2024-02-01	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000201983	SCV000303153	benign	not specified		criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000201983	SCV000592375	likely benign	not specified	2016-08-04	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000201983	SCV000595801	benign	not specified	2021-03-30	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000129433	SCV000684867	benign	Hereditary cancer-predisposing syndrome	2014-12-04	criteria provided, single submitter	clinical testing
Mendelics	RCV000602167	SCV001136385	likely benign	Colorectal cancer, hereditary nonpolyposis, type 2	2019-05-28	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001703976	SCV001156599	benign	not provided	2023-10-03	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000602167	SCV001305705	uncertain significance	Colorectal cancer, hereditary nonpolyposis, type 2	2018-03-13	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. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001798263	SCV002042084	likely benign	Breast and/or ovarian cancer	2023-04-25	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000129433	SCV002528779	benign	Hereditary cancer-predisposing syndrome	2020-10-16	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000201983	SCV002552442	benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001703976	SCV002585968	likely benign	not provided	2024-04-01	criteria provided, single submitter	clinical testing	MLH1: BS2
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.	RCV000129433	SCV004228159	benign	Hereditary cancer-predisposing syndrome	2023-10-17	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000201983	SCV000257115	likely benign	not specified		no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000602167	SCV000734265	benign	Colorectal cancer, hereditary nonpolyposis, type 2		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000201983	SCV001800507	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000201983	SCV001809242	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	RCV000201983	SCV001906407	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV001703976	SCV001924677	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000201983	SCV001952897	benign	not specified		no assertion criteria provided	clinical testing