• Test code: 04733
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top tube
  • Alternate specimens:
    DNA or saliva/assisted saliva
  • Sample requirements
  • Request a sample kit

Invitae Townes-Brocks Syndrome Test

Test description

The Townes-Brocks Syndrome Test analyzes SALL1, a gene that is associated with Townes-Brocks syndrome (TBS), a multisystemic disorder present at birth. There is often considerable clinical overlap between the features associated with TBS and other disorders, such as VATER (VACTERL) association, which can make accurate diagnoses difficult in the absence of molecular testing.

Accurate diagnosis is important for patients with Townes-Brocks syndrome because renal impairment in the absence of other structural abnormalities can occur, requiring surveillance. Identification of a disease-causing variant can guide genetic counseling and inform recurrence-risk assessment.

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Primary panel (1 gene)

Townes-Brocks syndrome (TBS) is a multisystemic disorder that is characterized by hypoplastic ears, hearing loss, and anal, limb, renal, and heart anomalies. Congenital heart defects, genitourinary anomalies, and foot malformations have also been observed. The majority of individuals with TBS have no intellectual difficulties, but about 10% display mild or moderate cognitive impairment.

Approximately 64%–83% of patients with a strong clinical suspicion of TBS have a pathogenic variant in the SALL1 gene.

Townes-Brocks syndrome is inherited in an autosomal dominant pattern. Approximately 50% of cases are attributable to de novo pathogenic variants.

Pathogenic variants in SALL1 demonstrate complete penetrance with variable expressivity. Significant variability may be seen in the clinical presentation of those affected by TBS, even within families.

The prevalence of Townes-Brocks syndrome is estimated at 1 in 250,000, but the specific occurrence is difficult confirm due to the variable clinical presentation of this disorder and the degree of overlap with symptoms of other genetic syndromes.

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 in the transcript listed below. In addition, analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any specific limitations in the analysis of these genes are also listed in the table below.

Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
SALL1 NM_002968.2