NM_002386.4(MC1R):c.689C>T (p.Pro230Leu) AND Melanoma, cutaneous malignant, susceptibility to, 5

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 26, 2023
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:: RCV001211146.8

Allele description [Variation Report for NM_002386.4(MC1R):c.689C>T (p.Pro230Leu)]

NM_002386.4(MC1R):c.689C>T (p.Pro230Leu)

Gene:

MC1R:melanocortin 1 receptor [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16q24.3

Genomic location:

Preferred name:

NM_002386.4(MC1R):c.689C>T (p.Pro230Leu)

HGVS:

NC_000016.10:g.89919947C>T
NG_012026.1:g.7069C>T
NG_027810.1:g.2939C>T
NM_002386.4:c.689C>TMANE SELECT
NP_002377.4:p.Pro230Leu
NC_000016.9:g.89986355C>T
NM_002386.3:c.689C>T

Protein change:

P230L

Links:

dbSNP: rs368714912

NCBI 1000 Genomes Browser:

rs368714912

Molecular consequence:

NM_002386.4:c.689C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Melanoma, cutaneous malignant, susceptibility to, 5
Synonyms:: Cutaneous malignant melanoma 5
Identifiers:: MONDO: MONDO:0013133; MedGen: C2751295; Orphanet: 618; OMIM: 613099

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001382671	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 26, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 11511307, 15998953, 22095472, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001382671

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 26, 2023)

germline

clinical testing

PubMed (4)
[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

Melanocortin 1 receptor (MC1R) gene variants are associated with an increased risk for cutaneous melanoma which is largely independent of skin type and hair color.

Kennedy C, ter Huurne J, Berkhout M, Gruis N, Bastiaens M, Bergman W, Willemze R, Bavinck JN.

J Invest Dermatol. 2001 Aug;117(2):294-300.

PubMed [citation]

PMID:: 11511307

MC1R, ASIP, and DNA repair in sporadic and familial melanoma in a Mediterranean population.

Landi MT, Kanetsky PA, Tsang S, Gold B, Munroe D, Rebbeck T, Swoyer J, Ter-Minassian M, Hedayati M, Grossman L, Goldstein AM, Calista D, Pfeiffer RM.

J Natl Cancer Inst. 2005 Jul 6;97(13):998-1007. Erratum in: J Natl Cancer Inst. 2005 Sep 21;97(18):1385.

PubMed [citation]

PMID:: 15998953

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001382671.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 230 of the MC1R protein (p.Pro230Leu). This variant is present in population databases (rs368714912, gnomAD 0.03%). This missense change has been observed in individual(s) with melanoma (PMID: 11511307, 15998953, 22095472). ClinVar contains an entry for this variant (Variation ID: 941371). 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 MC1R protein function with a negative predictive value of 95%. 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.

#	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: Sep 29, 2024

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