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, 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
SALL1 NM_002968.2