Diagnostic testing:
- Positive newborn screening for cblC defect (provide copy of newborn screening result, if available)
- Biochemical analysis indicative for cblC defect (provide copy of biochemical results)
Carrier testing:
- At least one affected or carrier relative
- Partner is affected or carrier
This test detects sequence alterations (SNVs, indels) and copy number variants (CNVs) in the coding exons and flanking intronic regions (+/- 10 bp) of MMACHC (NM_015506.3)
Targeted regions are enriched using hybridization probes (IDT) and sequencing libraries are prepared using the Illumina DNA Prep with Enrichment kit. Paired-end massively parallel sequencing of 150-bp fragments is performed with an Illumina instrument. Sequences are aligned and compared to reference genome GRCh37. Sample identity is confirmed in parallel using Applied Biosystems™ SNaPshot™ Multiplex Kit. Variants are interpreted as per standards and guidelines in the field (PMID: 25741868). Clinically relevant copy number variants are confirmed by an orthogonal method (gap-PCR, TaqMan, MLPA or microarray).
Based on validation study results, this test achieves >99% analytical sensitivity and specificity for SNVs, indels and CNVs. A negative result does not rule out the possibility that a rare variant not detected by this assay is present in the individual. This test does not detect all possible variants in the gene tested. Unless explicitly specified, only coding exons and flanking intronic regions are covered by this assay. Furthermore, technically challenging variant types, such as large indels, small CNVs, complex rearrangements, low-complexity repeat associated, segmental duplication associated, and postzygotic variants, may not be detected (PMID: 34007000). Interpretation of results is highly dependent on the clinical and demographic information provided.
Only clinically relevant variations are reported. Variations that are benign/probably benign or of uncertain significance, with limited evidence of pathogenicity, are not reported.
Turnaround time: 4-6 weeks
Specimen accepted:
- 2 x 4 mL blood in EDTA tubes (purple top tube) – 2 mL for newborns
- DNA: min 10 ug
- Amniotic fluid: min 10 ml
- Direct CVS: min 10 mg direct villi
- Cultured amniocytes or CVS: 2 x T25 flasks (confluent)
- For any other sample type, contact the laboratory for testing availability
Submit your test request using our molecular genetics requisition.