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Amyotrophic Lateral Sclerosis (ALS) via the hnRNPA1 Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
HNRNPA1 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9967HNRNPA181479 81479,81479 $990 Order Options and Pricing

Pricing Comments

Testing run on PG-select capture probes includes CNV analysis for the gene(s) on the panel but does not permit the optional add on of exome-wide CNV analysis. Any of the NGS platforms allow reflex to other clinically relevant genes, up to whole exome or whole genome sequencing depending upon the base platform selected for the initial test.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

This test is also offered via a custom panel (click here) on our exome or genome backbone which permits the optional add on of exome-wide CNV or genome-wide SV analysis.

Turnaround Time

3 weeks on average for standard orders or 2 weeks on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.


Genetic Counselors


  • Sali Farhan, PhD

Clinical Features and Genetics

Clinical Features

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by a selective loss of motor neurons in the motor cortex, brain steam, and spinal cord (Tandan and Bradley 1985). The dysfunction and loss of these neurons results in rapid progressive muscle weakness, atrophy and ultimately paralysis of limb, bulbar and respiratory muscles. The mean age of onset of symptoms is about 55 years of age; most cases begin between 40 and 70 years of age. The annual incidence of ALS is 1-2 per 100,000 (Cleveland and Rothstein 2001).

The most common symptoms include twitching and cramping of muscles of the hands and feet, loss of motor control in the hands and arms, weakness and fatigue, tripping and falling. Symptoms usually begin with asymmetric involvement of the muscles. As the disease progresses, symptoms may include difficulty in talking, breathing and swallowing, shortness of breath, and paralysis.

Cognitive impairment has not been initially associated with ALS. However, frontotemporal dementia (FTD) has been reported in several cases. Dementia has been documented in patients with ALS from different ethnic groups and affects both males and females (Wikström et al. 1982; Lipton, et al. 2004; Mitsuyama and Inoue 2009).


About 10% of ALS cases are familial (Emery and Holloway 1982). In most of these families, ALS is inherited in an autosomal dominant manner (AD-ALS) and is age-dependent with high penetrance. In rare families, the disease is transmitted in an autosomal recessive or dominant X-linked pattern.

About 90% of patients with ALS are sporadic cases (SALS) with no known affected relatives. It is unclear how many of the apparently sporadic cases are inherited with low penetrance. The clinical presentations of familial ALS (FALS) and sporadic ALS (SALS) are similar. However, the onset of symptoms in FALS is usually earlier compared to that of SALS (Kinsley and Siddique 2012).

Autosomal Dominant ALS (AD-ALS) is a clinically and genetically heterogeneous disorder that affects all ethnic groups. Several genes have been implicated in the disease including C9orf72, SOD1, FUS, TARDBP, ANG, OPTN, VCP, VAPB, and PFN1.

Recently, two heterozygous missense variants in the hnRNPA1 gene were identified, by whole exome sequencing, in patients with ALS. The first, (c.940G>A, p. Asp314Asn), occurred in one family with a history of autosomal dominant ALS and no pathogenic variants in the known ALS genes (Kim et al. 2013). Evidence for pathogenicity included its co-segregation with the disease; its absence from the NHLB1 Exome Sequencing Project; its location in an evolutionary conserved region of the protein; and a predicted deleterious effect by PolyPhen. The second variant, (c.956A>G, p.Asn319Ser), occurred in a sporadic case, and was reported as probably pathogenic (Kim et al. 2013).

The heterogeneous nuclear ribonucleoprotein hnRNPA1 is involved in mRNA metabolism through interactions with TDP-43, which is known to be involved in the pathogenesis of ALS (Buratti et al. 2005). Pathological studies revealed reductions of hnRNPA1 protein level accompanied by an aggregation of TDP-43 in motor neurons of spinal cord samples from autopsied patients with ALS, compared to that of controls (Honda et al. 2015)

Clinical Sensitivity - Sequencing with CNV PG-Select

Pathogenic variants in the hnRNPA1 gene appear to be a rare cause of ALS. To date, only two missense variants have been reported in patients with ALS; one of which is reported as probably pathogenic (Kim et al. 2013). More recent studies confirmed the earlier findings. No pathogenic HNRNPA1 variants were identified among Dutch and French cohorts of patients with ALS and ALS-FTD, with no causative variants in the remaining ALS genes (Seelen et al. 2014; Le Ber et al. 2014).

Testing Strategy

This test provides full coverage of all coding exons of the hnRNPA1 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

Patients with symptoms suggestive of ALS or Motor Neuron Disease, and no pathogenic variants in the C9orf72, SOD1, FUS, TARDBP, ANG, OPTN, VCP, PFN1, and VAPB genes.


Official Gene Symbol OMIM ID
HNRNPA1 164017
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Amyotrophic Lateral Sclerosis Type 20 AD 615426

Related Tests

Amyotrophic Lateral Sclerosis / Motor Neuron Disease via the FUS Gene
Amyotrophic Lateral Sclerosis via the ANG Gene
Amyotrophic Lateral Sclerosis via the OPTN Gene
Amyotrophic Lateral Sclerosis/Motor Neuron Disease via the TARDBP Gene


  • Buratti E. et al. 2005. The Journal of Biological Chemistry. 280: 37572-84. PubMed ID: 16157593
  • Cleveland D.W., Rothstein J.D. 2001. Nature Reviews. Neuroscience. 2: 806-19. PubMed ID: 11715057
  • Emery A.E., Holloway S. 1982. Advances in Neurology. 36: 139-47. PubMed ID: 7180680
  • Honda H. et al. 2015. Neuropathology : Official Journal of the Japanese Society of Neuropathology. 35: 37-43. PubMed ID: 25338872
  • Kim HJ. et al. 2013. Nature. 495: 467-73. PubMed ID: 23455423
  • Kinsley L, Siddique T. 2015 Amyotrophic Lateral Sclerosis Overview. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong C-T, and Stephens K, editors. GeneReviews™, Seattle (WA): University of Washington, Seattle. PubMed ID: 20301623
  • Le Ber I. et al. 2014. Neurobiology of Aging. 35: 934.e5-6. PubMed ID: 24119545
  • Lipton A.M. et al. 2004. Acta Neuropathologica. 108: 379-85. PubMed ID: 15351890
  • Mitsuyama Y., Inoue T. 2009. Neuropathology : Official Journal of the Japanese Society of Neuropathology. 29: 649-54. PubMed ID: 19780984
  • Seelen M. et al. 2014. Neurobiology of Aging. 35: 1956.e9-1956.e11. PubMed ID: 24612671
  • Tandan R., Bradley W.G. 1985. Annals of Neurology. 18: 271-80. PubMed ID: 4051456
  • Wikström J. et al. 1982. Archives of Neurology. 39: 681-3. PubMed ID: 7125994


Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page

If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.

Specimen Types

Specimen Requirements and Shipping Details

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