Submissions for variant NM_024996.7(GFM1):c.568A>C (p.Met190Leu)

gnomAD frequency: 0.00510  dbSNP: rs75450876

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000125226	SCV000168667	benign	not specified	2013-01-08	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.
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000224632	SCV000281196	likely benign	not provided	2015-06-04	criteria provided, single submitter	clinical testing	Converted during submission to Likely benign.
Illumina Laboratory Services, Illumina	RCV000368039	SCV000441854	benign	Hepatoencephalopathy due to combined oxidative phosphorylation defect type 1	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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000224632	SCV000885509	likely benign	not provided	2017-08-14	criteria provided, single submitter	clinical testing	The p.Met190Leu variant (rs75450876; ClinVar variation ID: 137465) has not been reported in the medical literature in association with disease. It is found with an allele frequency in African populations of 1.8% (423/24,024 alleles) in the Genome Aggregation Database. The methionine at codon 190 is moderately conserved and computational analyses (SIFT, PolyPhen-2) predict that this variant is tolerated. Based on available information, this variant is considered to be likely benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000224632	SCV001106477	benign	not provided	2025-01-15	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000224632	SCV005260944	likely benign	not provided		criteria provided, single submitter	not provided
Natera, Inc.	RCV000368039	SCV002081589	benign	Hepatoencephalopathy due to combined oxidative phosphorylation defect type 1	2019-10-21	no assertion criteria provided	clinical testing