Congenital Stationary Night Blindness and Retinal Degeneration via the SLC24A1 Gene - Clinical Genetic Test - GTR

Congenital Stationary Night Blindness and Retinal Degeneration via the SLC24A1 … see more Congenital Stationary Night Blindness and Retinal Degeneration via the SLC24A1 Gene see less

Clinical Genetic Test

offered by

PreventionGenetics, part of Exact Sciences

View lab's test page

GTR Test Accession: GTR000529324.13

INHERITED DISEASEOPHTHALMOLOGYNERVOUS SYSTEM ... View more

Last updated in GTR: 2020-09-11

View version history

GTR000529324.13, last updated: 2020-09-11

GTR000529324.12, last updated: 2020-09-09

GTR000529324.11, last updated: 2019-04-05

GTR000529324.10, last updated: 2018-12-05

GTR000529324.9, last updated: 2018-07-03

GTR000529324.8, last updated: 2018-06-13

GTR000529324.7, last updated: 2017-12-04

GTR000529324.6, last updated: 2017-03-13

GTR000529324.5, last updated: 2017-01-03

GTR000529324.4, last updated: 2016-04-18

GTR000529324.3, last updated: 2016-03-30

GTR000529324.2, last updated: 2016-03-08

GTR000529324.1, registered in GTR: 2016-02-02

Last annual review date for the lab: 2024-05-20

At a Glance

Test purpose:

Diagnosis; Mutation Confirmation; Pre-symptomatic; ...

Conditions (1):

Congenital stationary night blindness 1D

Genes (1):

SLC24A1 (15q22.31)

Methods (3):

Molecular Genetics - Deletion/duplication analysis: Next-Generation (NGS)/Massively parallel sequencing (MPS); ...

Target population:

Patients with symptoms suggestive of inherited optic neuropathy in CSNB …

Clinical validity:

Not provided

Clinical utility:

Not provided

Ordering Information

Offered by:

PreventionGenetics, part of Exact Sciences
View lab's website
View lab's test page

Specimen Source:

Cell culture
Fetal blood
Fibroblasts
Fresh tissue
Isolated DNA
Peripheral (whole) blood
White blood cell prep
View specimen requirements

Who can order:

Genetic Counselor
Health Care Provider
Licensed Physician

Test Order Code:

11671
View other test codes

Contact Policy:

Laboratory can only accept contact from health care providers. Patients/families are encouraged to discuss genetic testing options with their health care provider.

How to Order:

Please visit Lab website for details. Additional specimen types may be acceptable based on method. Please contact us about prenatal cases.
Order URL

Test service:

Clinical Testing/Confirmation of Mutations Identified Previously
    OrderCode: 11671
Custom Deletion/Duplication Testing
    OrderCode: 11671
Custom Sequence Analysis
    OrderCode: 100, 200, 300
Maternal cell contamination study (MCC)
    OrderCode: 800

Test additional service:

Custom Prenatal Testing
OrderCode: 990

Test development:

Test developed by laboratory (no manufacturer test name)

Informed consent required:

Pre-test genetic counseling required:

Post-test genetic counseling required:

Recommended fields not provided:

Lab contact for this test, Test strategy

Conditions

Total conditions: 1

Condition/Phenotype	Identifier

Test Targets

Genes

Total genes: 1

Gene	Associated Condition	Germline or Somatic	Allele (Lab-provided)	Variant in NCBI

Methodology

Total methods: 3

Method Category

Test method

Instrument

Deletion/duplication analysis

Next-Generation (NGS)/Massively parallel sequencing (MPS)

Other

Sequence analysis of the entire coding region

Next-Generation (NGS)/Massively parallel sequencing (MPS)

Other

Targeted variant analysis

Bi-directional Sanger Sequence Analysis

Applied Biosystems 3730 capillary sequencing instrument

Clinical Information

Test purpose:

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

Target population:

Patients with symptoms suggestive of inherited optic neuropathy in CSNB or retinal degeneration are candidates. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in SLC24A1.

Variant Interpretation:

What is the protocol for interpreting a variation as a VUS?
The PreventionGenetics protocol for interpreting sequence variants has been carefully developed over a period of 10 years. We are conservative in our interpretations. We do not label a variant as pathogenic or benign without conclusive evidence. Although we use a variety of software to assist us in interpretation, we rely … View more

Are family members with defined clinical status recruited to assess significance of VUS without charge?
Yes. Please visit our website for details at https://www.preventiongenetics.com/forms.php for Targeted variant tests.

Will the lab re-contact the ordering physician if variant interpretation changes?
Yes. Please visit our website for details http://preventiongenetics.com/

Recommended fields not provided:

Clinical validity, Clinical utility, Is research allowed on the sample after clinical testing is complete?, Sample negative report, Sample positive report

Technical Information

Test Procedure:

For PGxome® we use Next Generation Sequencing (NGS) technologies to cover the coding regions of targeted genes plus 10 bases of flanking non-coding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. As required, genomic DNA is … For PGxome® we use Next Generation Sequencing (NGS) technologies to cover the coding regions of targeted genes plus 10 bases of flanking non-coding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. As required, genomic DNA is extracted from patient specimens. Patient DNA corresponding to these regions is captured using Agilent Clinical Research Exome hybridization probes. Captured DNA is sequenced on the NovaSeq 6000 using 2x150 bp paired-end reads (Illumina, San Diego, CA, USA). The following quality control metrics are generally achieved: >97% of target bases are covered at >20x, and mean coverage of target bases >120x. Data analysis and interpretation is performed by the internally developed Infinity pipeline. Variant calls are made by the GATK haplotype caller (through Sentieon) and annotated using in house software and Jannovar. For Sanger sequencing, polymerase chain reaction (PCR) is used to amplify targeted regions. After purification of the PCR products, cycle sequencing is carried out using the ABI Big Dye Terminator v.3.0 kit. PCR products are resolved by electrophoresis on an ABI 3730xl capillary sequencer. In nearly all cases, cycle sequencing is performed separately in both the forward and reverse directions. Copy number variants (CNVs) are also detected from NGS data. We utilize a CNV calling algorithm that compares mean read depth and distribution for each target in the test sample against multiple matched controls. Neighboring target read depth and distribution and zygosity of any variants within each target region are used to reinforce CNV calls. All CNVs are confirmed using another technology such as aCGH, MLPA, or PCR before they are reported. Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please contact us (clinicaldnatesting@preventiongenetics.com) for Test Code, pricing, and turnaround time information. If the Sanger option is selected, CNV detection may be ordered through Test #600. View more

Availability:

Tests performed
Entire test performed in-house

Analytical Validity:

As of March 2016, 6.36 Mb of sequence (83 genes, 1557 exons) generated in our lab was compared between Sanger and NextGen methodologies. We detected no differences between the two methods. The comparison involved 6400 total sequence variants (differences from the reference sequences). Of these, 6144 were nucleotide substitutions and … As of March 2016, 6.36 Mb of sequence (83 genes, 1557 exons) generated in our lab was compared between Sanger and NextGen methodologies. We detected no differences between the two methods. The comparison involved 6400 total sequence variants (differences from the reference sequences). Of these, 6144 were nucleotide substitutions and 256 were insertions or deletions. About 65% of the variants were heterozygous and 35% homozygous. The insertions and deletions ranged in length from 1 to over 100 nucleotides. In silico validation of insertions and deletions in 20 replicates of 5 genes was also performed. The validation included insertions and deletions of lengths between 1 and 100 nucleotides. Insertions tested in silico: 2200 between 1 and 5 nucleotides, 625 between 6 and 10 nucleotides, 29 between 11 and 20 nucleotides, 25 between 21 and 49 nucleotides, and 23 at or greater than 50 nucleotides, with the largest at 98 nucleotides. All insertions were detected. Deletions tested in silico: 1813 between 1 and 5 nucleotides, 97 between 6 and 10 nucleotides, 32 between 11 and 20 nucleotides, 20 between 21 and 49 nucleotides, and 39 at or greater than 50 nucleotides, with the largest at 96 nucleotides. All deletions less than 50 nucleotides in length were detected, 13 greater than 50 nucleotides in length were missed. Our standard NextGen sequence variant calling algorithms are generally not capable of detecting insertions (duplications) or heterozygous deletions greater than 100 nucleotides. Large homozygous deletions appear to be detectable. The PGxome test detects most larger deletions and duplications including intragenic CNVs and large cytogenetic events; however aberrations in a small percentage of regions may not be accurately detected due to sequence paralogy (e.g., pseudogenes, segmental duplications), sequence properties, deletion/duplication size (e.g., 1-3 exons vs. 4 or more exons), and inadequate coverage. In general, sensitivity for single, double, or triple exon CNVs is ~70% and for CNVs of four exon size or larger is >95%, but may vary from gene-to-gene based on exon size, depth of coverage, and characteristics of the region. View more

Proficiency testing (PT):

Is proficiency testing performed for this test?
Yes

Method used for proficiency testing:
Intra-Laboratory

VUS:

Software used to interpret novel variations
GeneSplicer, Human Splicing Finder, MaxEntScan, Mutation Taster, NNSPLICE, PolyPhen 2, SIFT and Splice Site Finder.

Laboratory's policy on reporting novel variations
Sequence variants found in our patients are contributed to ClinVar. Anonymous patient sequence data will also be shared with researchers for preparation of peer-reviewed publications.

Recommended fields not provided:

Test Confirmation, Assay limitations, Description of internal test validation method, Citations for Analytical validity, PT Provider, Description of PT method, Major CAP category, CAP category, CAP test list

Regulatory Approval

FDA Review:

Category: FDA exercises enforcement discretion

Additional Information

Reviews:

PubMed Clinical Queries

Clinical resources:

Molecular resources:

View SLC24A1 variations in ClinVar

Coriell Institute for Medical Research

Consumer resources:

Genetic Alliance

MalaCards

MedlinePlusGenetics (GHR)

NCATS Office of Rare Diseases Research (GARD)

MedlinePlus

IMPORTANT NOTE: NIH does not independently verify information submitted to GTR; it relies on submitters to provide information that is accurate and not misleading. NIH makes no endorsements of tests or laboratories listed in GTR. GTR is not a substitute for medical advice. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.