Submissions for variant NM_001040108.2(MLH3):c.2221G>T (p.Val741Phe)

gnomAD frequency: 0.02049  dbSNP: rs28756990

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000005901	SCV000388776	likely benign	Colorectal cancer, hereditary nonpolyposis, type 7	2017-04-27	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.
Invitae	RCV000005901	SCV000562032	benign	Colorectal cancer, hereditary nonpolyposis, type 7	2024-01-31	criteria provided, single submitter	clinical testing
Mendelics	RCV000986164	SCV001135069	benign	not provided	2019-05-28	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV001698939	SCV002551434	benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV001698939	SCV002727444	benign	not specified	2020-07-30	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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000986164	SCV004562830	benign	not provided	2023-11-22	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000986164	SCV004699408	benign	not provided	2023-12-01	criteria provided, single submitter	clinical testing	MLH3: BP4, BS1, BS2
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV001698939	SCV004848643	benign	not specified	2022-03-30	criteria provided, single submitter	clinical testing	The c.2221G>T (p.Val741Phe) variant in MLH3 is classified as benign since it has ben identified in 5% of African chromosomes in gnomAD, including 35 homozygotes. ACMG/AMP Criteria_ BA1.
OMIM	RCV000005900	SCV000026082	pathogenic	Endometrial carcinoma	2007-07-15	no assertion criteria provided	literature only
OMIM	RCV000005901	SCV000026083	pathogenic	Colorectal cancer, hereditary nonpolyposis, type 7	2007-07-15	no assertion criteria provided	literature only
Clinical Genetics, Academic Medical Center	RCV001698939	SCV001919263	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001698939	SCV001926422	benign	not specified		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001698939	SCV002036587	benign	not specified		no assertion criteria provided	clinical testing