Submissions for variant NM_000249.3(MLH1):c.-93G>A

gnomAD frequency: 0.22121  dbSNP: rs1800734

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT)	RCV000075069	SCV000106959	no known pathogenicity	Lynch syndrome	2013-09-05	reviewed by expert panel	research	MAF >1%
Ambry Genetics	RCV000215209	SCV000272940	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.
PreventionGenetics, part of Exact Sciences	RCV000250465	SCV000303142	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000018636	SCV000443321	benign	Colorectal cancer, hereditary nonpolyposis, type 2	2018-03-06	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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Invitae	RCV001513671	SCV001721324	benign	Hereditary nonpolyposis colorectal neoplasms	2024-01-19	criteria provided, single submitter	clinical testing
GeneDx	RCV001596951	SCV001832004	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 27895767, 31530880, 24325908, 25804231, 25421847, 30093976, 22878509, 28195176, 26275295, 15382050, 22371642, 23226285, 24205329, 21206982, 21348638, 24689082, 17374836, 19956916, 18712731, 18405947, 18523027, 23374646, 20060799, 21565826, 23621208, 20860725)
Fulgent Genetics, Fulgent Genetics	RCV002477216	SCV002795943	benign	Mismatch repair cancer syndrome 1; Muir-Torré syndrome; Colorectal cancer, hereditary nonpolyposis, type 2	2022-05-02	criteria provided, single submitter	clinical testing
OMIM	RCV000018636	SCV000038919	uncertain significance	Colorectal cancer, hereditary nonpolyposis, type 2	2007-02-15	no assertion criteria provided	literature only
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000250465	SCV001931232	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000250465	SCV001952916	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	RCV000250465	SCV002034332	benign	not specified		no assertion criteria provided	clinical testing