NM_002386.4(MC1R):c.537dup (p.Ile180fs) AND Melanoma, cutaneous malignant, susceptibility to, 5

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 1, 2024
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:: RCV000527730.10

Allele description [Variation Report for NM_002386.4(MC1R):c.537dup (p.Ile180fs)]

NM_002386.4(MC1R):c.537dup (p.Ile180fs)

Gene:

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

Variant type:

Duplication

Cytogenetic location:

16q24.3

Genomic location:

Preferred name:

NM_002386.4(MC1R):c.537dup (p.Ile180fs)

HGVS:

NC_000016.10:g.89919795dup
NG_012026.1:g.6917dup
NG_027810.1:g.2787dup
NM_002386.4:c.537dupMANE SELECT
NP_002377.4:p.Ile180fs
NP_002377.4:p.Ile180fs
NC_000016.9:g.89986202_89986203insC
NC_000016.9:g.89986203dup
NM_002386.3:c.537dup
NM_002386.3:c.537dupC

Protein change:

I180fs

Links:

dbSNP: rs555179612

NCBI 1000 Genomes Browser:

rs555179612

Molecular consequence:

NM_002386.4:c.537dup - frameshift variant - [Sequence Ontology: SO:0001589]

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

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
SCV000648549	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 1, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000648549

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 1, 2024)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

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, SCV000648549.9

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

Description

This sequence change creates a premature translational stop signal (p.Ile180Hisfs*59) in the MC1R gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 138 amino acid(s) of the MC1R protein. This variant is present in population databases (rs555179612, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with MC1R-related conditions. This variant is also known as 537insC. ClinVar contains an entry for this variant (Variation ID: 470706). 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

ClinVar

Relating variation to medicine