This test analyzes the SMARCA4 gene. Pathogenic variants in SMARCA4 are associated with small cell carcinoma of the ovary hypercalcemic type (SCCOHT) and rhabdoid tumor predisposition syndrome type 2 (RTPS).
Genetic testing of this gene 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.
SMARCA4 can also be ordered as part of a broader panel to test for different types of hereditary cancer conditions. Depending on the individual’s clinical and family history, one of these broader panels may be appropriate. Any of these broader panels can be ordered at no additional charge.
Small cell carcinoma of the ovary hypercalcemic type (SCCOHT) is a specific type of ovarian cancer that can be distinguished from others by the presence of hypercalcemia (seen in one-third of cases), early age of onset (average 25 years), and small, hyperchromatic cells with brisk mitotic activity. SCCOHT can be difficult to differentiate from other ovarian cancers because there is significant pathology overlap with sex cord-stromal tumors, germ cell tumors, endometrial stromal sarcoma, and neuroblastoma—among others. It has been suggested that SCCOHT is a rhabdoid tumor and should be referred to as malignant rhabdoid tumor of the ovary (MRTO).
Individuals with a pathogenic variant in SMARCA4 have an increased risk of malignancy compared to the average person, but not everyone with a pathogenic variant will actually develop cancer. Further, the same variant can present differently, even among family members. The lifetime risks for SCCOHT in individuals with a pathogenic SMARCA4 variant is currently unclear.
SCCOHT can occur in isolation, but approximately 50% of cases are due to heritable pathogenic variants in the SMARCA4 gene.
SCCOHT is inherited in an autosomal dominant pattern, but it is uncommon for the condition to actually be inherited from a parent. Most cases of SCCOHT occur as the result of a spontaneous de novo mutation.
SCCOHT accounts for less than 1% of all ovarian cancer. Approximately 50% of SCCOHT cases are due to pathogenic variants in the SMARCA4 gene.
Genetic testing of the SMARCA4 gene is reasonable to consider for any individual with a personal and/or family history of any of the following:
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|