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  • Test code: 55010
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top EDTA tube (K2EDTA or K3EDTA)
  • Alternate specimens:
    Saliva, assisted saliva, buccal swab and gDNA
  • Sample requirements
  • Request a sample kit
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Invitae Limb and Digital Malformations Panel

Test description

The Invitae Limb and Digital Malformations Panel analyzes genes that are associated with conditions affecting the limbs and/or digits. These are genetically heterogeneous disorders characterized by abnormal limb and/or digit development or growth. The genetic heterogeneity associated with these conditions can make it difficult to use phenotype as the sole criterion to select a definitive cause. 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 and provide information for recurrence-risk estimation and genetic counseling. The hand-foot-genital syndrome-associated polyalanine repeat expansions in HOXA13 are not currently analyzed by this assay.

CEP290: Analysis includes the intronic variant NM_025114.3:c.2991+1655A>G.

RBM8A: Analysis includes the non-coding variants NM_005105.4:c.-21G>A and c.67+32G>C.

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Primary panel (178 genes)

ACVR1 ADAMTS10 ADAMTS17 AFF4 AHI1 ANKRD11 ARHGAP31 ARID1A ARID1B ARL13B ARL6 B3GLCT B9D1 B9D2 BBS1 BBS10 BBS12 BBS2 BBS4 BBS5 BBS7 BBS9 BHLHA9 BMP2 BMP4 BMPR1B BTRC C2CD3 CACNA1C CC2D2A CCNQ CDH3 CEP104 CEP120 CEP290 CEP41 CHSY1 CHUK CKAP2L CPLANE1 CREBBP CSPP1 DDX59 DHCR7 DHODH DLL4 DLX5 DLX6 DOCK6 DPF2 DVL1 DVL3 DYNC1I1 EOGT EP300 ESCO2 EVC EVC2 FAT1 FBLN1 FBN1 FBXW4 FGF10 FGF9 FGFR1 FGFR2 FGFR3 FIG4 FLNA FMN1 FRAS1 FREM2 FZD2 GDF5 GDF6 GJA1 GLI2 GLI3 GNAS GSC HDAC4 HDAC8 HOXA13 HOXD13 IFT57 IHH INPP5E KDM6A KIAA0586 KIF7 KMT2A KMT2D LMBR1 LRP4 LTBP2 LTBP3 MAP3K20 MEGF8 MGP MKKS MKS1 MRE11 MYCN NECTIN1 NECTIN4 NIPBL NOG NOTCH1 NPHP1 NPHP3 NSDHL NXN OFD1 PDE3A PDE4D PDE6D PGM3 PHF6 PIGV PIK3CA PITX1 POLR1A PORCN PRKAR1A PRMT7 PTDSS1 PTHLH RAB23 RAD21 RBM8A RBPJ RECQL4 ROR2 RPGRIP1L SALL1 SALL4 SC5D SDCCAG8 SF3B4 SMAD4 SMARCA2 SMARCA4 SMARCB1 SMARCE1 SMC1A SMC3 SMOC1 SOST SOX11 SOX9 TBX15 TBX3 TBX5 TCTN1 TCTN2 TCTN3 TGDS THPO TMEM107 TMEM138 TMEM216 TMEM231 TMEM237 TMEM67 TP63 TRIM32 TRPS1 TRPV4 TTC21B TTC8 VAC14 WDPCP WNT10B WNT3 WNT5A WNT7A ZNF423 ZSWIM6

  • Acheiropodia
  • Acrocapitofemoral dysplasia
  • Acrodysostosis
  • Acrofacial dysostosis 1, Nager type
  • Acromelic frontonasal dysostosis
  • Acromesomelic dysplasia
  • Acroscyphodysplasia
  • Adams-Oliver syndrome
  • Albright’s Hereditary Osteodystrophy (pseudopseudohypoparathyroidism)
  • Bardet-Biedl syndrome
  • Borjeson-Forssman-Lehmann syndrome
  • Brachydactyly
  • Campomelic dysplasia
  • Carpenter syndrome
  • Catel-Manzke syndrome
  • Cenani-Lenz syndactyly syndrome
  • CHILD syndrome
  • CHOPS syndrome
  • Cleft lip/palate-ectodermal dysplasia syndrome
  • Cocoon syndrome
  • Coffin-Siris syndrome
  • Cornelia de Lange syndrome
  • Cousin syndrome
  • Culler-Jones syndrome
  • Duane-radial ray syndrome and acro-renal-ocular syndrome
  • Ectodermal dysplasia-syndactyly syndrome
  • EEM syndrome
  • Ellis-van Creveld syndrome
  • Colobomatous microphthalmia, ptosis, and cutaneous syndactyly with or without glomerulotubular nephropathy
  • Feingold syndrome
  • Apert syndrome and Jackson-Weiss syndrome
  • Fibrodysplasia ossificans progressiva
  • Filippi syndrome
  • Focal dermal hypoplasia (Goltz-Gorlin syndrome)
  • Fraser syndrome
  • Geleophysic dysplasia
  • Polydactyly
  • Greig cephalopolysyndactyly syndrome
  • Hand-foot genital syndrome/Guttmacher syndrome
  • Hartsfield syndrome
  • Hereditary thrombocythemia
  • Holt-Oram syndrome
  • Hyperphosphatasia with intellectual disability
  • Hypertension and brachydactyly syndrome
  • Joubert syndrome
  • Kabuki syndrome
  • KBG syndrome
  • Keipert syndrome
  • Keutel syndrome
  • Acrocallosal syndrome and hydrolethalus syndrome
  • Lacrimo-auriculo-dento-digital (LADD) syndrome
  • Lathosterolosis
  • Lenz-Majewski hyperostosis syndrome
  • LTBP3-related dental anomalies and short stature
  • Meckel syndrome
  • Mesoaxial synostotic syndactyly with phalangeal reduction
  • Miller syndrome
  • Multiple synostoses syndrome
  • Myhre syndrome
  • Nicolaides-Baraitser syndrome
  • NOG-related symphalangism spectrum disorder
  • Oculodentodigital dysplasia
  • Omodysplasia
  • Ophthalmo-acromelic syndrome
  • Oral-facial-digital syndrome (orofaciodigital syndrome)
  • Otopalatodigital spectrum disorders
  • Pallister-Hall syndrome
  • Peters-plus syndrome
  • PGM3-congenital disorder of glycosylation
  • PIK3CA-related overgrowth spectrum (PROS)
  • RECQL4-related disorders (including Rothmund-Thomson syndrome, RAPADILINO syndrome and Baller-Gerold syndrome)
  • Roberts-SC phocomelia syndrome
  • Robinow syndrome
  • Rubinstein-Taybi syndrome
  • Short stature, auditory canal atresia, mandibular hypoplasia, and skeletal abnormalities
  • Short stature, brachydactyly, intellectual developmental disability, and seizures (SBIDDS)
  • Smith-Lemli-Opitz syndrome
  • SOST-related sclerosing bone dysplasias (including sclerosteosis and van Buchem disease)
  • Split hand/foot malformation
  • STAR syndrome
  • Symphalangism
  • Synpolydactyly
  • Temtamy preaxial brachydactyly syndrome
  • Short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies
  • Thrombocytopenia absent radius syndrome
  • Timothy syndrome
  • Townes-Brocks syndrome
  • TP63-related conditions (including ectrodactyly, ectodermal dysplasia, cleft lip/palate (EEC) syndrome, ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome, acro-dermo-ungual-lacrimal-tooth (ADULT) syndrome, and limb-mammary syndrome)
  • Trichorhinophalangeal syndrome
  • TRPV4-related conditions (including brachyolmia, metatropic dysplasia, digital arthropathy-brachydactyly, and spondylometaphyseal dysplasia, Kozlowski or Maroteaux type)
  • Ulnar-mammary syndrome
  • Weill-Marchesani syndrome
  • Weill-Marchesani-like syndrome
  • Wiedemann-Steiner syndrome
  • WNT7A-related conditions (including Fuhrmann syndrome, Al-Awadi-Raas Rothschild syndrome, and Santos syndrome)
  • Yunis-Varon syndrome

To view the complete clinical description of this panel, click here.

Limb and digital malformations can occur in several inheritance patterns including autosomal dominant, autosomal recessive, and X-linked.

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 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
ACVR1 NM_001105.4
ADAMTS10 NM_030957.3
ADAMTS17 NM_139057.3
AFF4 NM_014423.3
AHI1 NM_017651.4
ANKRD11 NM_013275.5
ARHGAP31 NM_020754.3
ARID1A NM_006015.4
ARID1B NM_020732.3
ARL13B NM_182896.2
ARL6 NM_177976.2
B3GLCT NM_194318.3
B9D1 NM_015681.3
B9D2 NM_030578.3
BBS1 NM_024649.4
BBS10 NM_024685.3
BBS12 NM_152618.2
BBS2 NM_031885.3
BBS4 NM_033028.4
BBS5 NM_152384.2
BBS7 NM_176824.2
BBS9* NM_198428.2
BHLHA9 NM_001164405.1
BMP2 NM_001200.3
BMP4 NM_001202.3
BMPR1B NM_001203.2
BTRC NM_033637.3
C2CD3 NM_015531.5; NM_001286577.1
CACNA1C NM_000719.6; NM_001129840.1
CC2D2A NM_001080522.2
CCNQ NM_152274.3
CDH3 NM_001793.5
CEP104 NM_014704.3
CEP120 NM_153223.3
CEP290* NM_025114.3
CEP41 NM_018718.2
CHSY1 NM_014918.4
CHUK NM_001278.4
CKAP2L NM_152515.4
CPLANE1 NM_023073.3
CREBBP NM_004380.2
CSPP1 NM_024790.6
DDX59 NM_001031725.5
DHCR7 NM_001360.2
DHODH NM_001361.4
DLL4 NM_019074.3
DLX5 NM_005221.5
DLX6 NM_005222.3
DOCK6 NM_020812.3
DPF2 NM_006268.4
DVL1 NM_004421.2
DVL3 NM_004423.3
DYNC1I1 NM_004411.4
EOGT NM_173654.2
EP300 NM_001429.3
ESCO2 NM_001017420.2
EVC NM_153717.2
EVC2 NM_147127.4
FAT1 NM_005245.3
FBLN1 NM_006486.2
FBN1 NM_000138.4
FBXW4 NM_022039.3
FGF10 NM_004465.1
FGF9 NM_002010.2
FGFR1 NM_023110.2
FGFR2 NM_000141.4
FGFR3 NM_000142.4
FIG4 NM_014845.5
FLNA NM_001456.3
FMN1 NM_001103184.3; NM_001277314.1
FRAS1 NM_025074.6
FREM2 NM_207361.5
FZD2 NM_001466.3
GDF5 NM_000557.4
GDF6 NM_001001557.2
GJA1 NM_000165.4
GLI2 NM_005270.4
GLI3 NM_000168.5
GNAS NM_000516.5
GSC NM_173849.2
HDAC4 NM_006037.3
HDAC8 NM_018486.2
HOXA13 NM_000522.4
HOXD13 NM_000523.3
IFT57 NM_018010.3
IHH NM_002181.3
INPP5E NM_019892.4
KDM6A NM_021140.3
KIAA0586 NM_001244189.1
KIF7 NM_198525.2
KMT2A NM_001197104.1
KMT2D NM_003482.3
LMBR1 NM_022458.3
LRP4 NM_002334.3
LTBP2 NM_000428.2
LTBP3 NM_001130144.2
MAP3K20 NM_016653.2
MEGF8* NM_001410.2
MGP NM_000900.3
MKKS NM_018848.3
MKS1 NM_017777.3
MRE11 NM_005591.3
MYCN NM_005378.5
NECTIN1 NM_002855.4
NECTIN4 NM_030916.2
NIPBL* NM_133433.3
NOG NM_005450.4
NOTCH1 NM_017617.3
NPHP1 NM_000272.3
NPHP3 NM_153240.4
NSDHL NM_015922.2
NXN NM_022463.4
OFD1 NM_003611.2
PDE3A NM_000921.4
PDE4D NM_001104631.1
PDE6D NM_002601.3
PGM3 NM_001199917.1
PHF6 NM_032458.2
PIGV NM_017837.3
PIK3CA NM_006218.2
PITX1 NM_002653.4
POLR1A NM_015425.4
PORCN NM_203475.2
PRKAR1A NM_002734.4
PRMT7 NM_019023.2
PTDSS1 NM_014754.2
PTHLH NM_198965.1
RAB23 NM_183227.2
RAD21 NM_006265.2
RBM8A* NM_005105.4
RBPJ NM_005349.3
RECQL4* NM_004260.3
ROR2 NM_004560.3
RPGRIP1L NM_015272.2
SALL1 NM_002968.2
SALL4 NM_020436.3
SC5D NM_006918.4
SDCCAG8 NM_006642.3
SF3B4 NM_005850.4
SMAD4 NM_005359.5
SMARCA2 NM_003070.4
SMARCA4 NM_001128849.1
SMARCB1 NM_003073.3
SMARCE1 NM_003079.4
SMC1A NM_006306.3
SMC3 NM_005445.3
SMOC1 NM_001034852.2
SOST NM_025237.2
SOX11 NM_003108.3
SOX9 NM_000346.3
TBX15 NM_152380.2
TBX3 NM_005996.3
TBX5 NM_000192.3
TCTN1 NM_001082538.2
TCTN2 NM_024809.4
TCTN3 NM_015631.5
TGDS NM_014305.3
THPO NM_000460.3
TMEM107 NM_032354.3
TMEM138 NM_016464.4
TMEM216 NM_001173990.2
TMEM231 NM_001077416.2
TMEM237 NM_001044385.2
TMEM67 NM_153704.5
TP63 NM_003722.4
TRIM32 NM_012210.3
TRPS1 NM_014112.4
TRPV4 NM_021625.4
TTC21B NM_024753.4
TTC8 NM_198309.3
VAC14 NM_018052.3
WDPCP NM_015910.5
WNT10B NM_003394.3
WNT3 NM_030753.4
WNT5A NM_003392.4
WNT7A NM_004625.3
ZNF423 NM_015069.3
ZSWIM6 NM_020928.1

BBS9: Deletion/duplication analysis is not offered for exon 4.
CEP290: Analysis includes the intronic variant NM_025114.3:c.2991+1655A>G.
MEGF8: Sequencing analysis for exons 39 includes only cds +/- 10 bp.
NIPBL: Sequencing analysis is not offered for exon 33.
RBM8A: Analysis includes the non-coding variants NM_005105.4:c.-21G>A and c.67+32G>C.
RECQL4: Sequencing analysis for exons 13-14 is limited to cds +/-10 bp.