Diagnosis; Mutation Confirmation; Pre-symptomatic; Prognostic; Risk Assessment; Screening

For patients suspected to this particular and patients with positive familial history for this disease, gene sequence analysis is recommended as the first step in mutation identification.

DNA is extracted from the patient specimen, PCR amplification and sequence analysis of the entire coding region/ or indicated exons plus additional flanking intronic or other non-coding sequence. Sanger sequencing is carried out and the sequence is visualised on a capillary sequencer. Sequencing is performed separately in both the forward … DNA is extracted from the patient specimen, PCR amplification and sequence analysis of the entire coding region/ or indicated exons plus additional flanking intronic or other non-coding sequence. Sanger sequencing is carried out and the sequence is visualised on a capillary sequencer. Sequencing is performed separately in both the forward and reverse directions. View more

confirmation of identified mutations in an independent experiment

Tests performed
Entire test performed in-house

This test detects >99% of described mutations

Is proficiency testing performed for this test? Help
Yes

Method used for proficiency testing: Help
Formal PT program

PT Provider: Help
European Molecular Genetics Quality Network, EMQN

Description of PT method: Help
For Proficiency Testing, both external and internal, we have Sanger-sequenced extensive number of PCR fragments, and the error rate is less than 0.01% (99.99% accuracy). Also We had performed MLPA large numbers of samples, and NGS (used for increasing number of genes and panels in cardiogenetics, metabolic diseases, ophthalmogenetics and … For Proficiency Testing, both external and internal, we have Sanger-sequenced extensive number of PCR fragments, and the error rate is less than 0.01% (99.99% accuracy). Also We had performed MLPA large numbers of samples, and NGS (used for increasing number of genes and panels in cardiogenetics, metabolic diseases, ophthalmogenetics and rare diseases) with the maximal possible technical accuracy (>99,8%). Technical specificity for methods used in our lab is estimated > 99,5% and technical sensitivity > 99,5%. Mutation detection reproducibility for Sanger sequencing is near to 100%. In the past other methods with lower accuracy and sensitivity such as SSCP, dHPLC were used. However because of the superior quality of these methods, we completely switched to the above mentioned methods. View more

Software used to interpret novel variations Help
Alamut (Interactive Biosoftware), including AGVGD, PolyPhen-2, SIFT and MutationTaster for missense predictions and MAXEntScan, NNSPLICE, GeneSplicer and Human Splicing Finder for splice predictions

Laboratory's policy on reporting novel variations Help
Our laboratory reports class 3 (unknown pathogenicity), class 4 (likely pathogenic) and class 5 (certainly pathogenic) variants.