This test analyzes the MET gene, which is associated with hereditary papillary renal cell carcinoma (HPRCC). This highly penetrant, rare, autosomal-dominant condition causes a predisposition to developing type 1 papillary renal cell carcinoma that is typically bilateral and multifocal. HPRCC is an adult-onset condition with an average age of onset of 50 years.
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.
The general population risk of developing kidney cancer is approximately 1.6%. Papillary renal cell carcinoma (PRCC) accounts for 10%–20% of all renal cell cancers. Although most cases are sporadic, it is believed that 1%-4% of renal cancers are due to an underlying hereditary cancer syndrome. A small but currently unknown number of these hereditary cases is due to hereditary papillary renal cell carcinoma (HPRCC). This highly penetrant, rare, autosomal-dominant condition is associated with a predisposition to developing type 1 papillary renal cell carcinoma that is typically bilateral and multifocal. There are no other organ systems or clinical features associated with this condition. HPRCC is an adult-onset condition with an average age of onset of 50 years.
Most individuals with a pathogenic variant in MET will express the condition and manifest symptoms of HPRCC. The lifetime risk of renal cancer for individuals with HPRCC approaches 100%.
Most cases are inherited in an autosomal dominant pattern, although the rate of spontaneous de novo mutations is unknown.
Individuals—particularly adults—presenting with papillary renal carcinoma may be considered for analysis of the MET gene.
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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|