Submissions for variant NM_000249.4(MLH1):c.589-15C>T

gnomAD frequency: 0.00582  dbSNP: rs55658850

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT)	RCV000030229	SCV000106788	likely benign	Lynch syndrome	2013-09-05	reviewed by expert panel	research	MAF >1% in African population
PreventionGenetics, part of Exact Sciences	RCV000202179	SCV000303151	benign	not specified		criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000580940	SCV000684846	benign	Hereditary cancer-predisposing syndrome	2015-04-13	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001145067	SCV001305702	likely benign	Colorectal cancer, hereditary nonpolyposis, type 2	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
GeneDx	RCV001355286	SCV001882139	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Invitae	RCV002054507	SCV002428570	benign	Hereditary nonpolyposis colorectal neoplasms	2024-02-01	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000580940	SCV002528756	benign	Hereditary cancer-predisposing syndrome	2020-02-06	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000202179	SCV002552431	benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000580940	SCV002653606	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.
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV001145067	SCV004015873	likely benign	Colorectal cancer, hereditary nonpolyposis, type 2	2023-07-07	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003492306	SCV004239263	benign	Breast and/or ovarian cancer	2022-07-12	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000030229	SCV000052896	benign	Lynch syndrome	2011-04-22	no assertion criteria provided	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000202179	SCV000257108	benign	not specified		no assertion criteria provided	research
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001355286	SCV001550124	uncertain significance	not provided		no assertion criteria provided	clinical testing