The Disorders of Somatic Mosaicism NGS Panel is a 56-gene panel intended for patients with a diagnosis or clinical suspicion of a disorder caused by mosaic variants in one of the genes listed below.
Arteriovenous malformation of the brain, Capillary malformations, Capillary Malformation-Arteriovenous Malformation Syndrome, Cardioacrofacial dysplasia, Cerebral cavernous malformations, CLAPO syndrome, CLOVE syndrome, Congenital smooth muscle hamartoma with or without hemihypertrophy\, somatic mosaic, Curry-Jones syndrome, Cushing syndrome\, ACTH-independent adrenal, D-2-hydroxyglutaric aciduria, Ectodermal dysplasia with facial dysmorphism and acral\, ocular\, and brain anomalies, Encephalocraniocutaneous lipomatosis, Epidermal nevus, Focal cortical dysplasias, Hemangioma\, capillary infantile, Hemifacial myohyperplasia, Hypereosinophilic syndrome\, idiopathic\, resistant to imatinib, Hypoinsulinemic hypoglycemia with hemihypertrophy, Keratosis\, seborrheic, Lymphatic malformations, Macrodactyly, McCune-Albright syndrome, Megalencephaly-capillary malformation-polymicrogyria syndrome, Melanocytic nevus syndrome, Melorheostosis\, isolated, Meningioma, Metaphyseal chondromatosis with increased urinary excretion of D-2-hydroxyglutarate, Neurocutaneous melanosis, Nevus sebaceous or woolly hair nevus, Oculoectodermal syndrome, Ollier disease/Maffucci syndrome, Phakomatosis pigmentovascularis and extensive dermal melanocytosis, PIK3CA-related overgrowth spectrum, Proteus syndrome, Schimmelpenning-Feuerstein-Mims syndrome, Schwannomatosism Spitz nevus or nevus spilus, Sturge-Weber syndrome, Vascular malformations with and without overgrowth
This panel consists of 56 genes associated with different forms of disorders caused by somatic mosaicism, including somatic overgrowth, vascular tumors, venous or arteriovenous malformations, skin pigmentary mosaicism and dermal hypoplasia, and RASopathies.
This panel uses custom-baits to provide a higher depth of coverage for targeted genes than standard exome or genome sequencing, allowing it to identify variants of somatic origin that might otherwise be missed with traditional NGS technologies. A specific diagnosis can provide prognostic insights and guide treatment as well as facilitate monitoring for additional associated health concerns. A clear diagnosis also prevents further, unnecessary testing and gives valuable recurrence risk information.
Heterozygous germline variants may also be identified in addition to somatic changes. Phenotypes associated with heterozygous germline variants may differ from somatic/mosaic changes.
This panel is performed by NGS, and it covers all coding exons and 10-20 base pairs of intronic sequencing flanking each coding exon of the 56 genes tested. Additional specific intronic regions of interest are also included. This method allows for analysis of greater than 98% of the targeted sequence for the detection of nucleotide substitutions and small deletions and duplications. Reportable variants include pathogenic variants, likely pathogenic variants, and variants of uncertain significance.
The lower limit of detection of this assay is 2% variant allele frequency. Variants identified on the panel are confirmed with Sanger sequencing, digital PCR, and/or allele-specific PCR based on the type of alteration. The laboratory will determine the appropriate confirmation method. Alterations located outside of the targeted regions, such as promoter regions, untranslated regions, and other non-coding regions, are not otherwise interrogated. Large deletions and duplications, complex indels, structural variants, or copy number variants will not be detected by this panel. We recommend further testing to more accurately address any concerns of dosage alterations.
Most variants in the analyzed genes are somatic in origin, often occurring post-zygotically leading to mosaicism. These variants are better detected in affected tissue and are often poorly detected in the blood. Submission of affected tissue is strongly recommended to increase sensitivity. The testing price includes submitting up to two different sample types. Specifically, a primary sample will be run on the NGS panel, and a secondary sample, if submitted, can be used for targeted testing if an alteration is found in the primary sample.
The preferred sample will vary by patient depending on their clinical presentation. All of the following are acceptable sample types. Please contact the laboratory to discuss your patient if you have additional questions.
Call 1-800-473-9411 to speak with our team of laboratory genetic counselors for questions or additional information.
Robin Fletcher, MS, CGC
Falecia Thomas, MS, CGC
Alex Finley, MS, CGC