NM_005912.3(MC4R):c.20G>A (p.Arg7His) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 22, 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:: RCV003553894.2

Allele description [Variation Report for NM_005912.3(MC4R):c.20G>A (p.Arg7His)]

NM_005912.3(MC4R):c.20G>A (p.Arg7His)

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.20G>A (p.Arg7His)

HGVS:

NC_000018.10:g.60372330C>T
NG_016441.1:g.5439G>A
NM_005912.3:c.20G>AMANE SELECT
NP_005903.2:p.Arg7His
LRG_1346t1:c.20G>A
LRG_1346:g.5439G>A
LRG_1346p1:p.Arg7His
NC_000018.9:g.58039563C>T
NM_005912.2:c.20G>A

Protein change:

R7H

Molecular consequence:

NM_005912.3:c.20G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004297612	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 22, 2022)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 15489963, 20462274, 29311635, 31002796, 24611737, 29970488, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004297612

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 22, 2022)

germline

clinical testing

PubMed (7)
[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

Constitutive activity of the melanocortin-4 receptor is maintained by its N-terminal domain and plays a role in energy homeostasis in humans.

Srinivasan S, Lubrano-Berthelier C, Govaerts C, Picard F, Santiago P, Conklin BR, Vaisse C.

J Clin Invest. 2004 Oct;114(8):1158-64.

PubMed [citation]

PMID:: 15489963
PMCID:: PMC522250

Pharmacological characterization of 30 human melanocortin-4 receptor polymorphisms with the endogenous proopiomelanocortin-derived agonists, synthetic agonists, and the endogenous agouti-related protein antagonist.

Xiang Z, Proneth B, Dirain ML, Litherland SA, Haskell-Luevano C.

Biochemistry. 2010 Jun 8;49(22):4583-600. doi: 10.1021/bi100068u.

PubMed [citation]

PMID:: 20462274
PMCID:: PMC2888279

See all PubMed Citations (7)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004297612.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies have shown that this missense change affects MC4R function (PMID: 15489963, 20462274, 29311635, 31002796). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt MC4R protein function. This missense change has been observed in individual(s) with obesity (PMID: 24611737, 29970488). This variant is present in population databases (rs142837166, gnomAD 0.04%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 7 of the MC4R protein (p.Arg7His).

#	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

ClinVar

Relating variation to medicine