Submissions for variant NM_005912.3(MC4R):c.307G>A (p.Val103Ile)

gnomAD frequency: 0.01533  dbSNP: rs2229616

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000202600	SCV000409976	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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Personalized Diabetes Medicine Program, University of Maryland School of Medicine	RCV000445452	SCV000537109	benign	Monogenic diabetes	2019-01-18	criteria provided, single submitter	research	ACMG criteria: BP4 (REVEL 0.050 + 6 predictors; not using PP3/4 predictors), BA1 (overall MAF in gnomAD 1.6%; over 2% in multiple subpop), BS2 (51 homozygotes in gnomAD, 237 cases and 277 controls in type2diabetesgenetics.org)=benign
Labcorp Genetics (formerly Invitae), Labcorp	RCV002057039	SCV002403135	benign	not provided	2024-01-13	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV002057039	SCV005312069	benign	not provided		criteria provided, single submitter	not provided
UCL Genetics Institute, UCL	RCV000202600	SCV000257526	protective	Obesity	2014-12-23	no assertion criteria provided	case-control
Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital	RCV000202600	SCV000692298	uncertain significance	Obesity	2014-09-18	no assertion criteria provided	clinical testing
OMIM	RCV000768671	SCV000900038	benign	MELANOCORTIN 4 RECEPTOR POLYMORPHISM	1999-04-01	no assertion criteria provided	literature only
OMIM	RCV000768672	SCV000900039	protective	OBESITY, RESISTANCE TO	1999-04-01	no assertion criteria provided	literature only
Clinical Genetics, Academic Medical Center	RCV001699064	SCV001924236	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001699064	SCV001926975	benign	not specified		no assertion criteria provided	clinical testing
Imperial College London Diabetes Centre, Mubadala Healthcare	RCV001778791	SCV002014764	pathogenic	BODY MASS INDEX QUANTITATIVE TRAIT LOCUS 20	2020-05-01	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003977552	SCV004797497	benign	MC4R-related disorder	2021-11-08	no assertion criteria provided	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).