NM_005912.3(MC4R):c.812G>A (p.Cys271Tyr) AND Obesity due to melanocortin 4 receptor deficiency

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 1, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV004017248.1

Allele description [Variation Report for NM_005912.3(MC4R):c.812G>A (p.Cys271Tyr)]

NM_005912.3(MC4R):c.812G>A (p.Cys271Tyr)

Gene:

MC4R:melanocortin 4 receptor [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

18q21.32

Genomic location:

Preferred name:

NM_005912.3(MC4R):c.812G>A (p.Cys271Tyr)

HGVS:

NC_000018.10:g.60371538C>T
NG_016441.1:g.6231G>A
NM_005912.2(MC4R):c.812G>A
NM_005912.3:c.812G>AMANE SELECT
NP_005903.2:p.Cys271Tyr
LRG_1346t1:c.812G>A
LRG_1346:g.6231G>A
LRG_1346p1:p.Cys271Tyr
NC_000018.9:g.58038771C>T
NM_005912.2(MC4R):c.812G>A
NM_005912.2:c.812G>A
P32245:p.Cys271Tyr

Protein change:

C271Y; CYS271TYR

Links:

UniProtKB: P32245#VAR_038652; OMIM: 155541.0014; dbSNP: rs121913562

NCBI 1000 Genomes Browser:

rs121913562

Molecular consequence:

NM_005912.3:c.812G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Obesity due to melanocortin 4 receptor deficiency
Identifiers:: MONDO: MONDO:0019115; MedGen: C4273958

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004848247	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 1, 2022)	germline	clinical testing	PubMed (10) [See all records that cite these PMIDs] 20826565, 10903343, 12646665, 12959994, 12588803, 16752916, 17628007, 25332687, 18801902, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004848247

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Mar 1, 2022)

germline

clinical testing

PubMed (10)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Pharmacological chaperones restore function to MC4R mutants responsible for severe early-onset obesity.

René P, Le Gouill C, Pogozheva ID, Lee G, Mosberg HI, Farooqi IS, Valenzano KJ, Bouvier M.

J Pharmacol Exp Ther. 2010 Dec;335(3):520-32. doi: 10.1124/jpet.110.172098. Epub 2010 Sep 8.

PubMed [citation]

PMID:: 20826565

Dominant and recessive inheritance of morbid obesity associated with melanocortin 4 receptor deficiency.

Farooqi IS, Yeo GS, Keogh JM, Aminian S, Jebb SA, Butler G, Cheetham T, O'Rahilly S.

J Clin Invest. 2000 Jul;106(2):271-9.

PubMed [citation]

PMID:: 10903343
PMCID:: PMC314308

See all PubMed Citations (10)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV004848247.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (10)

Description

proposed classification - variant undergoing re-assessment, contact laboratory

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 13, 2024

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