NM_002386.4(MC1R):c.718G>A (p.Ala240Thr) AND Melanoma, cutaneous malignant, susceptibility to, 5

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 23, 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:: RCV001979889.4

Allele description [Variation Report for NM_002386.4(MC1R):c.718G>A (p.Ala240Thr)]

NM_002386.4(MC1R):c.718G>A (p.Ala240Thr)

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.718G>A (p.Ala240Thr)

HGVS:

NC_000016.10:g.89919976G>A
NG_012026.1:g.7098G>A
NG_027810.1:g.2968G>A
NM_002386.4:c.718G>AMANE SELECT
NP_002377.4:p.Ala240Thr
NC_000016.9:g.89986384G>A

Protein change:

A240T

Links:

dbSNP: rs778930648

NCBI 1000 Genomes Browser:

rs778930648

Molecular consequence:

NM_002386.4:c.718G>A - 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

Recent activity

Clear Turn Off Turn On

SHC SH2 domain-binding protein 1 [Mus musculus]
SHC SH2 domain-binding protein 1 [Mus musculus]
gi|6755508|ref|NP_035499.1|

Protein

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
SCV002223867	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 23, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 26800492, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002223867

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 23, 2022)

germline

clinical testing

PubMed (2)
[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

Characterization of patients at high risk of melanoma in Austria.

Müller C, Wendt J, Rauscher S, Burgstaller-Muehlbacher S, Sunder-Plassmann R, Scheurecker C, Richtig E, Fae I, Fischer G, Pehamberger H, Okamoto I.

Br J Dermatol. 2016 Jun;174(6):1308-17. doi: 10.1111/bjd.14407. Epub 2016 Apr 26.

PubMed [citation]

PMID:: 26800492

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002223867.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This missense change has been observed in individual(s) with melanoma (PMID: 26800492). This variant is present in population databases (rs778930648, gnomAD 0.01%). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 240 of the MC1R protein (p.Ala240Thr). ClinVar contains an entry for this variant (Variation ID: 1447574). 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.

#	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

ClinVar

Relating variation to medicine