ClinVar Miner

Submissions for variant NM_005912.3(MC4R):c.466C>T (p.Gln156Ter) (rs369841551)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine RCV000709738 SCV000840005 pathogenic Obesity 2017-01-18 criteria provided, single submitter clinical testing This c.466C>T (p.Gln156*) variant has not been observed in the ExAC database, nor has been observed in our patient cohort but has been reported in dbSNP (rs369841551) with a minor allele frequency of 0.00008. This c.466C>T encodes for a nonsense codon in exon 1 at amino acid position 156 of the MC4R protein. This premature stop codon is predicted to result in a loss of function of the protein. It is thus classify as a pathogenic variant.
Athena Diagnostics Inc RCV000681814 SCV000842716 pathogenic not provided 2018-02-19 criteria provided, single submitter clinical testing
Translational Genomics Laboratory,University of Maryland School of Medicine RCV000754806 SCV000882455 pathogenic Monogenic diabetes 2017-06-15 criteria provided, single submitter clinical testing The c.466C>T variant in codon 156 (exon 1) of the melanocortin 4 receptor gene, MC4R, results in the generation of a stop codon and the expected loss of four of the seven transmembrane domains of the protein (10592235). The c.466C>T variant was not observed in the NHLBI Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium databases. Nonsense mutations in MC4R have been reported previously as autosomal dominant, monogenic causes of obesity (10199800, 12646665). All individuals found to have pathogenic mutations in MC4R in one study had severe hyperinsulinemia, even compared to obese controls (12646665). The c.466C>T variant was previously identified in a 12-year old boy with severe early-onset obesity (27654141). Additionally, multiple lines of computational evidence (SIFT, LRT, MutationTaster, CADD, GERP) predict this variant is probably damaging to the protein structure or function. ACMG criteria = PVS1, PM2, PP3
Institute of Human Genetics, University of Leipzig Medical Center RCV001262853 SCV001440876 likely pathogenic BODY MASS INDEX QUANTITATIVE TRAIT LOCUS 20 2019-01-01 criteria provided, single submitter clinical testing
Gharavi Laboratory,Columbia University RCV000681814 SCV000809285 likely pathogenic not provided 2018-09-16 no assertion criteria provided research

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