Invitae Melanoma Panel


Test description

The Invitae Melanoma Panel analyzes up to 12 genes associated with a hereditary predisposition to melanoma. These genes were selected based on available evidence to provide Invitae’s most comprehensive test targeting hereditary melanoma.

Genetic testing of these genes may confirm a diagnosis and help guide treatment and management decisions. Identification of a disease-causing variant would also guide testing and diagnosis of at-risk relatives. This test is specifically designed for heritable germline mutations and is not appropriate for the detection of somatic mutations in tumor tissue.

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Primary panel (9 genes)


CDKN2A: Analysis supports interpretation of the p16 protein only
MITF: Analysis is limited to the NM_000248.3:c.952G>A p.Glu318Lys variant.
PTEN: Deletion/duplication analysis covers the promoter region.
TP53: Deletion/duplication analysis covers the promoter region.

Add-on preliminary-evidence genes (3 genes)

Preliminary-evidence genes currently have early evidence of a clinical association with the specific disease covered by this test. Some clinicians may wish to include genes which do not currently have a definitive clinical association, but which may prove to be clinically significant in the future. These genes can be added at no additional charge. Visit our Preliminary-evidence genes page to learn more.


  • hereditary melanoma
  • familial melanoma
  • malignant melanoma
  • cutaneous melanoma
  • uveal melanoma

Melanoma is a cancer of pigment-producing cells (melanocytes) that typically begins in the skin (cutaneous) but can also develop in eyes or organs. Most melanoma cells still make melanin, so melanoma tumors are usually brown or black, but some can appear pink, tan, or even white. Cutaneous melanomas can develop anywhere on the skin, but they are more likely to start on the trunk in men and on the legs in women. The neck and face are other common sites.

Dysplastic nevi are atypical moles that are benign but may resemble melanoma. These are associated with an increased risk of developing single or multiple melanomas. The higher the number of these moles an individual has, the higher the risk. Those who have 10 or more moles have 12 times the risk of developing melanoma compared to the general population. Individuals in melanoma-prone families frequently have these moles, which require close monitoring for any change in size, shape, or color—signs of malignant transformation.

Most cases of melanoma are isolated and sporadic. The number of individuals who have an inherited risk of melanoma is unknown, but it is thought to be low. An estimated 8% of individuals with melanoma also have a first-degree relative with melanoma and an estimated 1%–2% of people with melanoma have two or more affected close relatives.

Individuals with a pathogenic variant in one of these genes have an increased risk of malignancy compared to the average person, but not everyone with such a variant will develop cancer. Further, the same variant can cause different cancers, even among individuals within the same family. Because we cannot predict which cancers may develop, most who are found to have a pathogenic variant will be offered various screening tests to detect and prevent cancer. For gene-associated cancer risks, see the table below.

GeneMelanoma riskReferences (PMIDs)
BAP1 13% 26096145
BRCA2 elevated 10433620, 22187320
CDK4 elevated 25431349
CDKN2A 28%–67% 12072543, 16234560
MITF elevated 22080950, 22012259
POT1 elevated 24686846, 24686849
PTEN up to 6% 22252256
RB1 elevated 22355046
TP53 elevated 20522432

Elevated: There is evidence of association, but the penetrance and risk are not well characterized.

The genes on this panel confer an increased risk of developing melanoma in an autosomal dominant inheritance pattern. BRCA2 is also associated with autosomal recessive Fanconi anemia.

This panel may be considered for individuals with a personal and/or family history of melanoma (two or more affected first- or second-degree relatives). Additional features suggestive of a hereditary melanoma syndrome include a personal or family history of:

  • prostate, breast, ovarian, uterine, kidney, pancreatic, or mesothelioma
  • two or more primary melanomas or associated cancers in an individual
  • male breast cancer
  • breast or ovarian cancer and Ashkenazi Jewish ancestry
  • skin findings, such as multiple nevi

  1. American Cancer Society, What is melanoma skin cancer? Accessed September 2015.
  2. American Society of Clinical Oncology, Familial Malignant Melanoma,, Accessed September 2015.
  3. Aoude, LG, et al. Genetics of familial melanoma: 20 years after CDKN2A. Pigment Cell Melanoma Res. 2015; 28(2):148-60. doi: 10.1111/pcmr.12333. PMID: 25431349
  4. Begg, CB, et al. Lifetime risk of melanoma in CDKN2A mutation carriers in a population-based sample. J. Natl. Cancer Inst. 2005; 97(20):1507-15. doi: 10.1093/jnci/dji312. PMID: 16234564
  5. Bishop, DT, et al. Geographical variation in the penetrance of CDKN2A mutations for melanoma. J. Natl. Cancer Inst. 2002; 94(12):894-903. doi: 10.1093/jnci/94.12.894. PMID: 12072543
  6. Breast, Cancer, Linkage, Consortium. Cancer risks in BRCA2 mutation carriers. J. Natl. Cancer Inst. 1999; 91(15):1310-6. doi: 10.1093/jnci/91.15.1310. PMID: 10433620
  7. Gibbs, DC, et al. Inherited genetic variants associated with occurrence of multiple primary melanoma. Cancer Epidemiol. Biomarkers Prev. 2015; 24(6):992-7. PMID: 25837821
  8. Heidenreich, B, et al. TERT promoter mutations in cancer development. Curr. Opin. Genet. Dev. 2014; 24:30-7. PMID: 24657534
  9. Horn, S, et al. TERT promoter mutations in familial and sporadic melanoma. Science. 2013; 339(6122):959-61. PMID: 23348503
  10. Kleinerman, RA, et al. Variation of second cancer risk by family history of retinoblastoma among long-term survivors. J. Clin. Oncol. 2012; 30(9):950-7. PMID: 22355046
  11. Moran, A, et al. Risk of cancer other than breast or ovarian in individuals with BRCA1 and BRCA2 mutations. Fam. Cancer. 2012; 11(2):235-42. PMID: 22187320
  12. Rai, K, et al. Comprehensive review of BAP1 tumor predisposition syndrome with report of two new cases. Clin. Genet. 2015. PMID: 26096145
  13. Robles-Espinoza, CD, et al. POT1 loss-of-function variants predispose to familial melanoma. Nat. Genet. 2014; 46(5):478-81. PMID: 24686849
  14. Ruijs, MW, et al. TP53 germline mutation testing in 180 families suspected of Li-Fraumeni syndrome: mutation detection rate and relative frequency of cancers in different familial phenotypes. J. Med. Genet. 2010; 47(6):421-8. PMID: 20522432
  15. Shi, J, et al. Rare missense variants in POT1 predispose to familial cutaneous malignant melanoma. Nat. Genet. 2014; 46(5):482-6. PMID: 24686846
  16. Tan, MH, et al. Lifetime cancer risks in individuals with germline PTEN mutations. Clin. Cancer Res. 2012; 18(2):400-7. doi: 10.1158/1078-0432.CCR-11-2283. PMID: 22252256

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.

Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
BAP1 NM_004656.3
BRCA1 NM_007294.3
BRCA2 NM_000059.3
CDK4 NM_000075.3
CDKN2A* NM_000077.4, NM_058195.3
MC1R NM_002386.3
MITF* NM_000248.3
POT1 NM_015450.2
PTEN* NM_000314.4
RB1 NM_000321.2
TERT NM_198253.2
TP53* NM_000546.5

CDKN2A: Analysis supports interpretation of the p16 protein only
MITF: Analysis is limited to the NM_000248.3:c.952G>A p.Glu318Lys variant.
PTEN: Deletion/duplication analysis covers the promoter region.
TP53: Deletion/duplication analysis covers the promoter region.