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NM_002386.4(MC1R):c.662T>C (p.Ile221Thr) AND Melanoma, cutaneous malignant, susceptibility to, 5

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jan 26, 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:
RCV001882056.6

Allele description [Variation Report for NM_002386.4(MC1R):c.662T>C (p.Ile221Thr)]

NM_002386.4(MC1R):c.662T>C (p.Ile221Thr)

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.662T>C (p.Ile221Thr)
HGVS:
  • NC_000016.10:g.89919920T>C
  • NG_012026.1:g.7042T>C
  • NG_027810.1:g.2912T>C
  • NM_002386.4:c.662T>CMANE SELECT
  • NP_002377.4:p.Ile221Thr
  • NC_000016.9:g.89986328T>C
Protein change:
I221T
Links:
dbSNP: rs371906898
NCBI 1000 Genomes Browser:
rs371906898
Molecular consequence:
  • NM_002386.4:c.662T>C - 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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002163871Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Jan 26, 2022) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

CDKN2A mutations and MC1R variants in Italian patients with single or multiple primary melanoma.

Pastorino L, Bonelli L, Ghiorzo P, Queirolo P, Battistuzzi L, Balleari E, Nasti S, Gargiulo S, Gliori S, Savoia P, Abate Osella S, Bernengo MG, Bianchi ScarrĂ  G.

Pigment Cell Melanoma Res. 2008 Dec;21(6):700-9. doi: 10.1111/j.1755-148X.2008.00512.x. Epub 2008 Oct 22.

PubMed [citation]
PMID:
18983535

Role of key-regulator genes in melanoma susceptibility and pathogenesis among patients from South Italy.

Casula M, Muggiano A, Cossu A, Budroni M, Caracò C, Ascierto PA, Pagani E, Stanganelli I, Canzanella S, Sini M, Palomba G; Italian Melanoma Intergroup (IMI)., Palmieri G.

BMC Cancer. 2009 Oct 3;9:352. doi: 10.1186/1471-2407-9-352.

PubMed [citation]
PMID:
19799798
PMCID:
PMC2763007
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002163871.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. This missense change has been observed in individual(s) with melanoma (PMID: 18983535, 19799798). This variant is present in population databases (rs371906898, gnomAD 0.003%). This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 221 of the MC1R protein (p.Ile221Thr).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024