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Diagnoses of uncertain significance: kidney genetics in the 21st century

The increasing availability of sequencing has accelerated the discovery of genetic causes of kidney disease, with clear benefits for patients. However, insufficient or contradictory evidence exists for numerous variants that were previously reported to be pathogenic, calling into question some proposed gene–disease associations. Rigorous re-appraisal of evidence is needed to ensure diagnostic accuracy.

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  1. 1.

    MacArthur, D. G. et al. Nature 508, 469–476 (2014).

    CAS  Article  Google Scholar 

  2. 2.

    Richards, S. et al. Genet. Med. 17, 405–424 (2015).

    Article  Google Scholar 

  3. 3.

    Brnich, S. E. et al. Genome Med. 12, 3 (2019).

    Article  Google Scholar 

  4. 4.

    Sampson, M. G. et al. J. Am Soc. Nephrol. 27, 1970–1983 (2016).

    CAS  Article  Google Scholar 

  5. 5.

    Karim, Z. et al. N. Engl. J. Med. 359, 1128–1135 (2008).

    CAS  Article  Google Scholar 

  6. 6.

    Ashton, E. & Bockenhauer, D. Kidney Int. 97, 455–457 (2020).

    CAS  Article  Google Scholar 

  7. 7.

    Thompson, W. C. & Schumann, E. L. Law Human Behav. 11, 167–187 (1987).

    Article  Google Scholar 

  8. 8.

    Strande, N. T. et al. Am. J. Hum. Genet. 100, 895–906 (2017).

    CAS  Article  Google Scholar 

  9. 9.

    Levine, A. P. et al. J. Am. Soc. Nephrol. 31, 365–373 (2020).

    CAS  Article  Google Scholar 

  10. 10.

    Rehm, H. L. et al. N. Engl. J. Med. 372, 2235–2242 (2015).

    CAS  Article  Google Scholar 

Download references

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Correspondence to Matthew G. Sampson or Detlef Bockenhauer.

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The authors declare no competing interests.

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Gale, D.P., Mallett, A., Patel, C. et al. Diagnoses of uncertain significance: kidney genetics in the 21st century. Nat Rev Nephrol 16, 616–618 (2020).

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