The Invitae Comprehensive Neuropathies Panel analyzes genes that are associated with hereditary neuropathies, including but not limited to Charcot-Marie-Tooth disease (CMT), hereditary motor neuropathy (HMN), and hereditary sensory and autonomic neuropathy (HSAN). The genetic heterogeneity associated with these conditions can make it difficult to use phenotype as the sole criterion to select a definitive cause. These genes were curated based on the available evidence to date in order to provide analysis for hereditary neuropathies. Given the clinical overlap of hereditary neuropathies, broad panel testing allows for an efficient evaluation of several potential genes based on a single clinical indication. Some genes in this test may also be associated with additional unrelated disorders, which are not included in the list of disorders tested. Genetic testing of these genes may help confirm a clinical diagnosis, predict disease prognosis and progression, facilitate early detection of symptoms, inform family planning and genetic counseling, or promote enrollment in clinical trials.
AARS AIFM1 APOA1 ASAH1 ATL1 ATL3 ATP1A1 ATP7A BAG3 BICD2 BSCL2 CHCHD10 COX6A1 CYP27A1 CYP7B1 DCTN1 DHTKD1 DNAJB2 DNM2 DNMT1 DRP2 DST DYNC1H1 EGR2 ELP1 EXOSC9 FBLN5 FBXO38 FGD4 FIG4 GAN GARS GDAP1 GJB1 GLA GNB4 GSN HARS HEXA HINT1 HMBS HSPB1 HSPB8 IGHMBP2 INF2 KIF1A KIF5A LITAF LMNA LRSAM1 MARS MCM3AP MED25 MFN2 MME MORC2 MPZ MTMR2 NDRG1 NEFH NEFL NGF NTRK1 PDK3 PLEKHG5 PMP2 PMP22 POLG POLG2 PRDM12 PRPS1 PRX RAB7A REEP1 RETREG1 SBF1 SBF2 SCN11A SCN9A SEPT9 SH3TC2 SIGMAR1 SLC12A6 SLC25A46 SLC52A2 SLC52A3 SLC5A7 SMN1, SMN2 SPG11 SPTLC1 SPTLC2 SURF1 TFG TRIM2 TRPV4 TTR UBA1 VAPB VRK1 WNK1 YARS
ARHGEF10 CCT5 HSPB3 LAS1L MICAL1 SCN10A SGPL1 SLC25A21 SLC52A1
Preliminary-evidence genes currently have early evidence of a clinical association with the specific disease covered by this test. Some clinicians may wish to include genes which do not currently have a definitive clinical association, but which may prove to be clinically significant in the future.
AARS AIFM1 APOA1 ASAH1 ATL1 ATL3 ATP1A1 ATP7A BAG3 BICD2 BSCL2 CHCHD10 COX6A1 CYP27A1 CYP7B1 DCTN1 DHTKD1 DNAJB2 DNM2 DNMT1 DRP2 DST DYNC1H1 EGR2 ELP1 EXOSC9 FBLN5 FBXO38 FGD4 FIG4 GAN GARS GDAP1 GJB1 GLA GNB4 GSN HARS HEXA HINT1 HMBS HSPB1 HSPB8 IGHMBP2 INF2 KIF1A KIF5A LITAF LMNA LRSAM1 MARS MCM3AP MED25 MFN2 MME MORC2 MPZ MTMR2 NDRG1 NEFH NEFL NGF NTRK1 PDK3 PLEKHG5 PMP2 PMP22 POLG POLG2 PRDM12 PRPS1 PRX RAB7A REEP1 RETREG1 SBF1 SBF2 SCN11A SCN9A SEPT9 SH3TC2 SIGMAR1 SLC12A6 SLC25A46 SLC52A2 SLC52A3 SLC5A7 SMN1, SMN2 SPG11 SPTLC1 SPTLC2 SURF1 TFG TRIM2 TRPV4 TTR UBA1 VAPB VRK1 WNK1 YARS
Preliminary-evidence genes currently have early evidence of a clinical association with the specific disease covered by this test. Some clinicians may wish to include genes which do not currently have a definitive clinical association, but which may prove to be clinically significant in the future.
ARHGEF10 CCT5 HSPB3 LAS1L MICAL1 SCN10A SGPL1 SLC25A21 SLC52A1
Broad disorders tested:
Individual disorders tested:
To view the complete clinical description of this panel, click here.
Neuropathies can be inherited in an autosomal dominant, autosomal recessive, or X-linked pattern.
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 and 10 to 20 base pairs of adjacent intronic sequence on either side of the coding exons in the transcript listed below. In addition, the analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any limitations in the analysis of these genes will be listed on the report. Contact client services with any questions.
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 |
---|---|---|---|
AARS | NM_001605.2 | ||
AIFM1 | NM_004208.3 | ||
APOA1 | NM_000039.2 | ||
ARHGEF10 | NM_014629.3 | ||
ASAH1 | NM_177924.3 | ||
ATL1 | NM_015915.4 | ||
ATL3 | NM_015459.4 | ||
ATP1A1* | NM_000701.7 | ||
ATP7A | NM_000052.6 | ||
BAG3 | NM_004281.3 | ||
BICD2 | NM_001003800.1 | ||
BSCL2 | NM_032667.6 | ||
CCT5 | NM_012073.4 | ||
CHCHD10 | NM_213720.2 | ||
COX6A1 | NM_004373.3 | ||
CYP27A1 | NM_000784.3 | ||
CYP7B1 | NM_004820.3 | ||
DCTN1 | NM_004082.4 | ||
DHTKD1 | NM_018706.6 | ||
DNAJB2 | NM_001039550.1 | ||
DNM2 | NM_001005360.2 | ||
DNMT1 | NM_001130823.1 | ||
DRP2 | NM_001939.2 | ||
DST | NM_001723.5; NM_015548.4 | ||
DYNC1H1 | NM_001376.4 | ||
EGR2 | NM_000399.3 | ||
ELP1 | NM_003640.3 | ||
EXOSC9 | NM_001034194.1 | ||
FBLN5 | NM_006329.3 | ||
FBXO38 | NM_030793.4 | ||
FGD4 | NM_139241.3 | ||
FIG4 | NM_014845.5 | ||
GAN | NM_022041.3 | ||
GARS | NM_002047.2 | ||
GDAP1 | NM_018972.2 | ||
GJB1 | NM_000166.5 | ||
GLA* | NM_000169.2 | ||
GNB4 | NM_021629.3 | ||
GSN | NM_000177.4 | ||
HARS | NM_002109.5 | ||
HEXA | NM_000520.4 | ||
HINT1 | NM_005340.6 | ||
HMBS | NM_000190.3 | ||
HSPB1 | NM_001540.3 | ||
HSPB3 | NM_006308.2 | ||
HSPB8 | NM_014365.2 | ||
IGHMBP2 | NM_002180.2 | ||
INF2 | NM_022489.3 | ||
KIF1A | NM_004321.6 | ||
KIF5A | NM_004984.2 | ||
LAS1L | NM_031206.4 | ||
LITAF | NM_004862.3 | ||
LMNA | NM_170707.3 | ||
LRSAM1 | NM_138361.5 | ||
MARS | NM_004990.3 | ||
MCM3AP | NM_003906.4 | ||
MED25 | NM_030973.3 | ||
MFN2 | NM_014874.3 | ||
MICAL1 | NM_001286613.1 | ||
MME* | NM_007289.2 | ||
MORC2 | NM_001303256.2 | ||
MPZ | NM_000530.6 | ||
MTMR2 | NM_016156.5 | ||
NDRG1 | NM_006096.3 | ||
NEFH | NM_021076.3 | ||
NEFL | NM_006158.4 | ||
NGF | NM_002506.2 | ||
NTRK1 | NM_001012331.1 | ||
PDK3 | NM_001142386.2 | ||
PLEKHG5 | NM_020631.4 | ||
PMP2 | NM_002677.3 | ||
PMP22 | NM_000304.3 | ||
POLG | NM_002693.2 | ||
POLG2 | NM_007215.3 | ||
PRDM12 | NM_021619.2 | ||
PRPS1 | NM_002764.3 | ||
PRX | NM_181882.2 | ||
RAB7A | NM_004637.5 | ||
REEP1 | NM_022912.2 | ||
RETREG1 | NM_001034850.2 | ||
SBF1 | NM_002972.3 | ||
SBF2 | NM_030962.3 | ||
SCN10A | NM_006514.3 | ||
SCN11A* | NM_014139.2 | ||
SCN9A | NM_002977.3 | ||
SEPT9 | NM_006640.4 | ||
SGPL1 | NM_003901.3 | ||
SH3TC2 | NM_024577.3 | ||
SIGMAR1 | NM_005866.3 | ||
SLC12A6 | NM_133647.1 | ||
SLC25A21 | NM_030631.3 | ||
SLC25A46 | NM_138773.2 | ||
SLC52A1 | NM_017986.3 | ||
SLC52A2 | NM_024531.4 | ||
SLC52A3 | NM_033409.3 | ||
SLC5A7 | NM_021815.2 | ||
SMN1, SMN2* | NM_000344.3; NM_017411.3 | ||
SPG11 | NM_025137.3 | ||
SPTLC1 | NM_006415.3 | ||
SPTLC2 | NM_004863.3 | ||
SURF1 | NM_003172.3 | ||
TFG | NM_006070.5 | ||
TRIM2 | NM_001130067.1 | ||
TRPV4 | NM_021625.4 | ||
TTR | NM_000371.3 | ||
UBA1 | NM_003334.3 | ||
VAPB | NM_004738.4 | ||
VRK1 | NM_003384.2 | ||
WNK1 | NM_213655.4 | ||
YARS | NM_003680.3 |
ATP1A1: Deletion/duplication analysis is not offered for exon 1.
GLA: Analysis includes the intronic variant NM_000169.2:c.IVS4+919G>A.
MME: Deletion/duplication analysis is not offered for exons 3, 5-6.
SCN11A: Sequencing analysis for exons 1 includes only cds +/- 10 bp.
SMN1 or SMN2: The SMN1 gene is identical to the SMN2 gene with the exception of exon 8 (typically referred to as exon 7). This assay unambiguously detects SMN1 exon 8 copy number and sequence variants. Sequence variants outside of exon 8 will also be detected, but this assay cannot determine whether the variant is located in SMN1 or SMN2. SMN2 exon 8 copy number will be reported for individuals with a positive result in SMN1. CNVs of exons 1-7 of SMN1 or SMN2 (typically referred to as exons 1-6 in the literature) will not be reported. Variants in all exons with no evidence towards pathogenicity are not reported, but are available upon request. This assay cannot detect silent carriers (individuals that have 2 functional copies of SMN1 on one chromosome and zero copies on the other). Therefore a negative result for carrier testing greatly reduces but does not eliminate the chance that a person is a carrier. For individuals with 2 copies of SMN1, the residual risk of being a carrier has been reported to be 1 in 121 in African Americans, 1 in 345 in Ashkenazi Jewish individuals, 1 in 628 in Asians, 1 in 632 in Caucasians, and 1 in 1061 in Hispanic individuals (PMID: 23788250). The SMA-STAT test does not detect sequence variants in SMN1 or SMN2, and therefore cannot be used to identify compound heterozygotes.