Submissions for variant NM_002454.3(MTRR):c.66A>G (p.Ile22Met)

gnomAD frequency: 0.44947  dbSNP: rs1801394

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000126873	SCV000170402	benign	not specified	2013-08-26	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.
PreventionGenetics, part of Exact Sciences	RCV000126873	SCV000308884	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000264714	SCV000458420	benign	Disorders of Intracellular Cobalamin Metabolism	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001274255	SCV001720711	benign	Methylcobalamin deficiency type cblE	2025-02-03	criteria provided, single submitter	clinical testing
Pars Genome Lab	RCV001274255	SCV001745278	benign	Methylcobalamin deficiency type cblE	2021-06-19	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001274255	SCV002014291	benign	Methylcobalamin deficiency type cblE	2021-09-05	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV004716905	SCV005298603	benign	not provided		criteria provided, single submitter	not provided
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000126873	SCV005726735	likely benign	not specified	2024-11-11	criteria provided, single submitter	clinical testing
OMIM	RCV000007444	SCV000027644	risk factor	Neural tube defects, folate-sensitive, susceptibility to	2005-07-01	no assertion criteria provided	literature only
OMIM	RCV000007445	SCV000027645	risk factor	Down syndrome, susceptibility to	2005-07-01	no assertion criteria provided	literature only
Department of Pharmacy and Biotechnology, University of Bologna	RCV000144926	SCV000187683	uncertain significance	Gastrointestinal stromal tumor		no assertion criteria provided	case-control
Natera, Inc.	RCV001274255	SCV001458138	benign	Methylcobalamin deficiency type cblE	2020-09-16	no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000126873	SCV001924712	benign	not specified		no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000126873	SCV001963470	benign	not specified		no assertion criteria provided	clinical testing
Center of Excellence in Clinical Pharmacokinetics and Pharmacogenomics, Faculty of Medicine, Chulalongkorn University	RCV003482129	SCV004217840	drug response	Methotrexate response	2023-04-16	no assertion criteria provided	research	There was a significant risk of acute kidney injury at 24 hours after methotrexate administration intravenously with MTRR rs1801394 allele A compared to variant allele G (OR (95%CI) = 2.084 (1.001-4.301), p = 0.047.