Submissions for variant NM_005912.3(MC4R):c.751A>C (p.Ile251Leu)

gnomAD frequency: 0.00774  dbSNP: rs52820871

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000202590	SCV000409974	likely benign	Obesity	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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000419291	SCV000510930	likely benign	not provided	2016-12-02	criteria provided, single submitter	clinical testing	Converted during submission to Likely benign.
Personalized Diabetes Medicine Program, University of Maryland School of Medicine	RCV000445524	SCV000537107	benign	Monogenic diabetes	2019-01-25	criteria provided, single submitter	research	ACMG criteria: BP4 (REVEL 0.138 + 7 predictors), BA1 (1.1% in gnomAD ENF), BS2 (142 cases and 120 controls in type2diabetesgenetics.org); susceptibility factor with conflicting data (protective and obesity susceptibility), called polymorphism in multiple publications=benign
Genetic Services Laboratory, University of Chicago	RCV000501342	SCV000595714	likely benign	not specified	2017-05-12	criteria provided, single submitter	clinical testing
Athena Diagnostics Inc	RCV000419291	SCV000842719	benign	not provided	2017-12-22	criteria provided, single submitter	clinical testing
Invitae	RCV000419291	SCV001106702	benign	not provided	2024-01-17	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002500636	SCV002811825	benign	BODY MASS INDEX QUANTITATIVE TRAIT LOCUS 20	2021-08-29	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003977551	SCV004798478	benign	MC4R-related condition	2019-07-08	criteria provided, single submitter	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
UCL Genetics Institute, UCL	RCV000202590	SCV000257525	protective	Obesity	2014-12-23	no assertion criteria provided	case-control
Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital	RCV000202590	SCV000692301	uncertain significance	Obesity	2012-06-22	no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000501342	SCV001918873	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000501342	SCV001929009	benign	not specified		no assertion criteria provided	clinical testing