Submissions for variant NM_000249.4(MLH1):c.-28A>G

gnomAD frequency: 0.00110  dbSNP: rs56198082

Total submissions: 16

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000656855	SCV000149356	likely benign	not provided	2020-09-02	criteria provided, single submitter	clinical testing	Observed with MLH1 c.-7C>T and in isolation in individuals with MLH1-associated and other cancers (Lee 2005, Fredriksson 2006, Thompson 2014, Hesson 2015, Morak 2018, Lin 2019); Published functional studies are inconclusive: has not undergone independent functional interrogation, but when studied with MLH1 c.-7C>T, not associated with MLH1 promoter methylation and conflicting results regarding impact on MLH1 expression (Hesson 2015, Morak 2018); Case control studies suggest this variant is not associated with gastric cancer in a Chinese population (Zhi 2011); Observed in 0.1665% (471/282862) of alleles in large population cohorts (Lek 2016); This variant is associated with the following publications: (PMID: 30850667, 25762362, 24689082, 11726306, 22136435, 16963262, 15996210, 18726168, 18566915, 26888055, 29472279, 31386297)
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000115447	SCV000539630	benign	not specified	2016-03-28	criteria provided, single submitter	clinical testing	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: ExAC: 0.9% (58/6612) Finnish chromosomes
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000115447	SCV000592325	uncertain significance	not specified	2015-04-08	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000656855	SCV000691838	uncertain significance	not provided	2022-09-02	criteria provided, single submitter	clinical testing	BS1
Counsyl	RCV000662924	SCV000785872	likely benign	Colorectal cancer, hereditary nonpolyposis, type 2	2017-12-21	criteria provided, single submitter	clinical testing
Mendelics	RCV003492406	SCV000837989	likely benign	Hereditary cancer	2024-01-23	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000656855	SCV001153830	likely benign	not provided	2024-01-01	criteria provided, single submitter	clinical testing	MLH1: BP4, BS1
Illumina Laboratory Services, Illumina	RCV000662924	SCV001308677	uncertain significance	Colorectal cancer, hereditary nonpolyposis, type 2	2018-08-20	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.
Color Diagnostics, LLC DBA Color Health	RCV001190167	SCV001357593	likely benign	Hereditary cancer-predisposing syndrome	2018-11-15	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001521973	SCV001731416	benign	Hereditary nonpolyposis colorectal neoplasms	2022-12-06	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000115447	SCV002072436	uncertain significance	not specified	2019-07-09	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV001190167	SCV002528736	benign	Hereditary cancer-predisposing syndrome	2020-10-02	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000115447	SCV002552410	likely benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000115447	SCV002773900	benign	not specified	2021-09-20	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003149729	SCV003838265	likely benign	Breast and/or ovarian cancer	2022-11-11	criteria provided, single submitter	clinical testing
GenomeConnect, ClinGen	RCV000656855	SCV002074987	not provided	not provided		no assertion provided	phenotyping only	Variant interpreted as Uncertain significance and reported on 09-02-2020 by Lab or GTR ID 506138. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.