Skip to content
How It Works
Explore
Ask a Question Resources Pricing
Who It's For
Patients
Decode results, prep for appointments, weigh options.
Caregivers & advocates
Carry the research load for someone you love.
Providers & clinicians
Resources for patients in your practice.
Log In Sign Up
PubMed This is a summary of 20 peer-reviewed journal articles Updated
Neurology · Amyotrophic Lateral Sclerosis 24 (ALS24)

Navigating Genetic Testing and Family Risk in ALS24

At a Glance

A pathogenic or likely pathogenic NEK1 variant can increase susceptibility to ALS24 but does not guarantee that someone will develop ALS or predict when it might begin. Genetic counseling can help families understand results, testing choices, and privacy concerns.

When a genetic variant like NEK1 is identified, the focus often shifts from your own diagnosis to what this means for your children, siblings, and other biological relatives. Navigating these questions requires a balance of scientific understanding and emotional care. Because NEK1 is a “susceptibility gene” rather than a “deterministic” one, the implications for family members are complex and often require the guidance of a specialist [1][2].

Interpreting Your Genetic Report

Genetic test reports use a standardized five-tier system (ACMG/AMP guidelines) to describe how certain scientists are that a variant is linked to a disease [3]. Understanding where your result falls is the first step:

  • Pathogenic (P): There is very strong evidence that this specific variant causes an increased risk for ALS [4].
  • Likely Pathogenic (LP): There is a high probability that the variant is linked to the disease based on current evidence [3].
  • Variant of Uncertain Significance (VUS): This is a “maybe.” It means the laboratory found a change in the gene, but they do not yet have enough evidence to say if it is harmful or just a natural, benign variation [4][5]. A VUS should not be used to make medical decisions or for testing asymptomatic family members [6][7].
  • Likely Benign / Benign: These are considered normal variations and are not linked to ALS.

Note: “Likely Pathogenic” and “Pathogenic” are evidence categories. They do not quantify the penetrance or guarantee that an individual carrying the variant will develop ALS.

The Role of a Genetic Counselor

A certified genetic counselor is a vital member of your care team. Unlike a neurologist who focuses on your physical symptoms, a counselor focuses on the “map” of your family’s health [8]. They can:

  • Help you interpret the specific technical details of your report [9].
  • Explain the concept of incomplete penetrance—the fact that many people carry a NEK1 variant and never develop ALS [2][10].
  • Facilitate conversations with family members who may be anxious or confused about their own risk [11].
  • Discuss the legal and financial protections regarding genetic privacy and insurance in your specific region (as rules vary significantly by country) [12].

Testing Family Members: A Personal Choice

If you have a confirmed Pathogenic or Likely Pathogenic variant, your adult biological relatives may consider “predictive” or cascade testing to see if they also carry the variant [13].

Because NEK1 has incomplete penetrance and there is no proven preventative treatment, the clinical utility of this testing is limited. It is a deeply personal decision that should remain voluntary and involve several considerations:

  1. The Right Not to Know: Some relatives may prefer to live without the weight of this information [14][9].
  2. Uncertainty of Timing: Even if a relative carries the NEK1 variant, a positive test cannot predict if they will develop ALS, when it might start, or how severe it might be [15][16].
  3. Age of Testing: Clinical guidelines generally recommend against testing children for adult-onset conditions like ALS until they are old enough to make their own informed decision, as there is no childhood medical benefit [17].

Accessing and Sharing Your Records

You generally have the legal right to access your full genetic test results. To share this information with family members or their doctors, follow these steps:

  • Request the “Full Laboratory Report”: This is different from the summary letter your doctor might give you. It contains the specific “cDNA” and “protein” notation (e.g., NEK1 c.2434A>G) that other doctors need for accurate testing [10].
  • Use a Family Letter: Many genetic counselors can provide a “Dear Family” letter that explains the findings in plain language and lists the specific variant for their own physicians to reference [11].
  • Discuss Re-Analysis: Scientific understanding of genes changes over time. Ask your clinic or laboratory what their policy is for notifying patients if a VUS is upgraded or downgraded in the future [18][19].

By approaching genetic information with a specialist, you ensure that you and your family are making decisions based on the most accurate, current science while protecting your collective emotional well-being [20].

Common questions in this guide

What does a pathogenic NEK1 result mean for ALS24 risk?
A pathogenic or likely pathogenic NEK1 variant means the variant is linked to increased susceptibility to ALS24. It does not guarantee that the carrier will develop ALS, because not every person with a susceptibility variant is affected, and the result does not predict when disease would begin or how severe it would be.
What should I do if my NEK1 report says VUS?
A variant of uncertain significance, or VUS, means there is not enough evidence to know whether the genetic change is harmful or a normal variation. A VUS should not be used to make medical decisions or to test asymptomatic relatives; ask the laboratory or clinic how future reclassification will be communicated.
Should my adult relatives consider cascade testing for NEK1?
Adult biological relatives may choose predictive or cascade testing after a confirmed pathogenic or likely pathogenic result, but testing is voluntary and is best discussed with a certified genetic counselor. A positive result cannot predict whether, when, or how severely someone will develop ALS, and there is no proven preventive treatment.
Can ALS24 genetic testing predict whether or when I will develop ALS?
No. A NEK1 susceptibility result may change a person's risk, but it cannot determine whether ALS will occur, when symptoms might begin, or how severe the disease might be.
Should children be tested for a family NEK1 variant?
Clinical guidance generally recommends waiting to test children for adult-onset conditions such as ALS when there is no childhood medical benefit. They can make an informed decision about testing when they are old enough to understand the implications and choose for themselves.
How can I share my ALS24 genetic report with relatives or their doctors?
Request the full laboratory report rather than only a summary letter, because it includes the exact genetic notation needed for accurate testing. A genetic counselor may also provide a plain-language family letter that lists the variant for relatives and their healthcare professionals.
Does a NEK1 result rule out other genetic causes of ALS?
Not necessarily. The genes included in a test vary, so ask your clinician whether the testing included other relevant ALS genes, such as C9orf72, and whether additional testing or review of the results is appropriate.

Questions For You

Answer a question to get research tailored to you. Your answers are private.

Get notified when new evidence is published on amyotrophic lateral sclerosis, susceptibility to, 24.

We monitor PubMed for new peer-reviewed studies on this topic and email a short summary when something meaningful changes.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Based on my genetic report, is my NEK1 variant classified as 'Pathogenic,' 'Likely Pathogenic,' or a 'Variant of Uncertain Significance' (VUS)?
  2. 2.Was my test comprehensive enough to rule out other common ALS genes, like C9orf72, that might be acting alongside NEK1?
  3. 3.Can you refer me to a certified genetic counselor who has specific experience with adult-onset neurological conditions?
  4. 4.If a family member decides they want to be tested, what is the exact process for sharing my results with their healthcare provider?
  5. 5.Does the laboratory that performed my test have a policy for notifying patients if my variant is reclassified in the future?

References

References (20)
  1. 1

    NEK1 mutations and the risk of amyotrophic lateral sclerosis (ALS): a meta-analysis.

    Yao L, He X, Cui B, et al.

    Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 2021; (42(4)):1277-1285 doi:10.1007/s10072-020-05037-6.

    PMID: 33462636
  2. 2

    Current knowledge and recent insights into the genetic basis of amyotrophic lateral sclerosis.

    Volk AE, Weishaupt JH, Andersen PM, et al.

    Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V 2018; (30(2)):252-258 doi:10.1007/s11825-018-0185-3.

    PMID: 30220791
  3. 3

    Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

    Richards S, Aziz N, Bale S, et al.

    Genetics in medicine : official journal of the American College of Medical Genetics 2015; (17(5)):405-24 doi:10.1038/gim.2015.30.

    PMID: 25741868
  4. 4

    Quantifying the potential of functional evidence to reclassify variants of uncertain significance in the categorical and Bayesian interpretation frameworks.

    Brnich SE, Rivera-Muñoz EA, Berg JS

    Human mutation 2018; (39(11)):1531-1541 doi:10.1002/humu.23609.

    PMID: 30095857
  5. 5

    SOD-1 Variants in Amyotrophic Lateral Sclerosis: Systematic Re-Evaluation According to ACMG-AMP Guidelines.

    Ruffo P, Perrone B, Conforti FL

    Genes 2022; (13(3)) doi:10.3390/genes13030537.

    PMID: 35328090
  6. 6

    MaveMD: A functional data resource for genomic medicine.

    McEwen AE, Stone J, Tejura M, et al.

    medRxiv : the preprint server for health sciences 2025; doi:10.1101/2025.11.15.25336228.

    PMID: 41332838
  7. 7

    Emerging strategies for interpreting variants of uncertain significance (VUS) in amyotrophic lateral sclerosis.

    Ahmed M, Volkening K, Mclellan C, et al.

    Amyotrophic lateral sclerosis & frontotemporal degeneration 2026; 1-15 doi:10.1080/21678421.2026.2655734.

    PMID: 41989758
  8. 8

    Evidence-based consensus guidelines for ALS genetic testing and counseling.

    Roggenbuck J, Eubank BHF, Wright J, et al.

    Annals of clinical and translational neurology 2023; (10(11)):2074-2091 doi:10.1002/acn3.51895.

    PMID: 37691292
  9. 9

    Predictive genetic testing for amyotrophic lateral sclerosis and frontotemporal dementia: genetic counselling considerations.

    Crook A, Williams K, Adams L, et al.

    Amyotrophic lateral sclerosis & frontotemporal degeneration 2017; (18(7-8)):475-485 doi:10.1080/21678421.2017.1332079.

    PMID: 28585888
  10. 10

    Hand-onset weakness is a common feature of ALS patients with a NEK1 loss-of-function variant.

    Tsai YS, Lin KP, Jih KY, et al.

    Annals of clinical and translational neurology 2020; (7(6)):965-971 doi:10.1002/acn3.51064.

    PMID: 32462798
  11. 11

    How the prospect of a clinical trial impacts decision-making for predictive genetic testing in ALS.

    Fontaine M, Horowitz K, Anoja N, et al.

    Amyotrophic lateral sclerosis & frontotemporal degeneration 2025; (26(3-4)):343-351 doi:10.1080/21678421.2024.2423718.

    PMID: 39511709
  12. 12

    Reasons for and against presymptomatic genetic testing in frontotemporal dementia: a qualitative study.

    Graafland CH, Seelaar H, Panman JL, et al.

    Human genetics 2026; (145(1)):21 doi:10.1007/s00439-025-02795-1.

    PMID: 41697408
  13. 13

    Clinical Variant Reclassification in Hereditary Disease Genetic Testing.

    Kobayashi Y, Chen E, Facio FM, et al.

    JAMA network open 2024; (7(11)):e2444526 doi:10.1001/jamanetworkopen.2024.44526.

    PMID: 39504018
  14. 14

    Genetic screening in sporadic ALS and FTD.

    Turner MR, Al-Chalabi A, Chio A, et al.

    Journal of neurology, neurosurgery, and psychiatry 2017; (88(12)):1042-1044 doi:10.1136/jnnp-2017-315995.

    PMID: 28642287
  15. 15

    High Prevalence of SOD1 Pathogenic Variants in the UK Biobank: Implications for Early Intervention in Amyotrophic Lateral Sclerosis.

    Gagliardi D, Villella C, Zanovello M, et al.

    Annals of neurology 2026; (99(6)):1502-1515 doi:10.1002/ana.78195.

    PMID: 41852184
  16. 16

    TARDBP variants in Taiwanese ALS patients: Genetic spectrum, clinical features, and founder effects.

    Jih KY, Fang SY, Tsai YS, et al.

    Journal of the neurological sciences 2025; (474()):123531 doi:10.1016/j.jns.2025.123531.

    PMID: 40373480
  17. 17

    Human Genetics Society of Australasia Position Statement: Predictive and Presymptomatic Genetic Testing in Adults and Children.

    Vears DF, McLean A, La Spina C, et al.

    Twin research and human genetics : the official journal of the International Society for Twin Studies 2024; (27(2)):120-127 doi:10.1017/thg.2024.9.

    PMID: 38509872
  18. 18

    Reanalysis of eMERGE phase III sequence variants in 10,500 participants and infrastructure to support the automated return of knowledge updates.

    Zouk H, Yu W, Oza A, et al.

    Genetics in medicine : official journal of the American College of Medical Genetics 2022; (24(2)):454-462 doi:10.1016/j.gim.2021.10.010.

    PMID: 34906510
  19. 19

    Analysis of hereditary cancer gene variant classifications from ClinVar indicates a need for regular reassessment of clinical assertions.

    Davidson AL, Kondrashova O, Leonard C, et al.

    Human mutation 2022; (43(12)):2054-2062 doi:10.1002/humu.24468.

    PMID: 36095262
  20. 20

    Predictive genetic testing in amyotrophic lateral sclerosis (ALS): Experiences of decision-making and engagement with UK genetic counseling services.

    Howard J, Bekker HL, McDermott CJ, McNeill A

    Journal of genetic counseling 2026; (35(1)):e70184 doi:10.1002/jgc4.70184.

    PMID: 41714091

This page explains ALS24 and NEK1 family-risk testing for informational purposes only and does not constitute medical advice. A neurologist or certified genetic counselor can interpret your report and help your family consider testing.