Submissions for variant NM_000249.4(MLH1):c.198C>T (p.Thr66=)

gnomAD frequency: 0.00040  dbSNP: rs61751642

Total submissions: 16

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT)	RCV000075463	SCV000106460	likely benign	Lynch syndrome	2013-09-05	reviewed by expert panel	research	Synonymous substitution with no effect on splicing & MAF 0.01-1%
GeneDx	RCV000202044	SCV000170296	benign	not specified	2014-02-26	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.
Ambry Genetics	RCV000126776	SCV000212870	likely benign	Hereditary cancer-predisposing syndrome	2014-06-19	criteria provided, single submitter	clinical testing	This alteration is classified as likely 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001080685	SCV000252647	benign	Hereditary nonpolyposis colorectal neoplasms	2024-01-31	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000126776	SCV000684787	benign	Hereditary cancer-predisposing syndrome	2015-05-18	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000759812	SCV000889396	benign	not provided	2022-11-04	criteria provided, single submitter	clinical testing
Mendelics	RCV000987145	SCV001136368	likely benign	Colorectal cancer, hereditary nonpolyposis, type 2	2019-05-28	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000987145	SCV001310310	likely benign	Colorectal cancer, hereditary nonpolyposis, type 2	2017-08-16	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.
CeGaT Center for Human Genetics Tuebingen	RCV000759812	SCV001500300	likely benign	not provided	2023-07-01	criteria provided, single submitter	clinical testing	MLH1: BP4, BP7
Sema4, Sema4	RCV000126776	SCV002528701	likely benign	Hereditary cancer-predisposing syndrome	2020-10-13	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000202044	SCV002552413	likely benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003149736	SCV003838181	likely benign	Breast and/or ovarian cancer	2022-09-27	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV000075463	SCV004835250	benign	Lynch syndrome	2024-02-05	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000202044	SCV000257078	likely benign	not specified		no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000759812	SCV000592336	uncertain significance	not provided		no assertion criteria provided	clinical testing
True Health Diagnostics	RCV000126776	SCV000788022	likely benign	Hereditary cancer-predisposing syndrome	2018-02-20	no assertion criteria provided	clinical testing