ClinVar Miner

Submissions for variant NM_005912.3(MC4R):c.185A>G (p.Asn62Ser)

dbSNP: rs121913566
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV004017251 SCV004848250 likely pathogenic Obesity due to melanocortin 4 receptor deficiency 2018-09-28 criteria provided, single submitter clinical testing The p.Asn62Ser variant in MC4R has been reported in the homozygous state in 1 individual with severe obesity, and segregated with disease in 4 homozygous and 4 heterozygous affected relatives (Farooqi 2003, Farooqi 2003). Of note, the homozygous individuals in this family were more severely affected than the heterozygous individuals. This variant has been identified in 1/30782 South Asian chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org/). In vitro functional studies provide some evidence that the p.Asn62Ser variant may impact protein function (Tao 2003, Yeo 2003); however, these types of assays may not accurately represent biological function. Computational prediction tools and conservation analysis suggest that the p.Asn62Ser variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, although additional studies are required to fully establish its clinical significance, the p.Asn62Ser variant is likely pathogenic. ACMG/AMP Criteria applied: PM2, PP1_Moderate, PP3, PS3_Supporting.
OMIM RCV000015410 SCV000035671 pathogenic BODY MASS INDEX QUANTITATIVE TRAIT LOCUS 20 2003-03-20 no assertion criteria provided literature only

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