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. Author manuscript; available in PMC: 2015 Nov 1.
Published in final edited form as: Genet Med. 2015 Mar 5;17(5):405–424. doi: 10.1038/gim.2015.30

Table 5.

Rules for Combining Criteria to Classify Sequence Variants

Pathogenic
  1. 1 Very Strong (PVS1) AND
    1. ≥1 Strong (PS1–PS4) OR
    2. ≥2 Moderate (PM1–PM6) OR
    3. 1 Moderate (PM1–PM6) and 1 Supporting (PP1–PP5) OR
    4. ≥2 Supporting (PP1–PP5)

  2. ≥2 Strong (PS1–PS4) OR

  3. 1 Strong (PS1–PS4) AND
    1. ≥3 Moderate (PM1–PM6) OR
    2. 2 Moderate (PM1–PM6) AND ≥2 Supporting (PP1–PP5) OR
    3. 1 Moderate (PM1–PM6) AND ≥4 Supporting (PP1–PP5)
Likely Pathogenic

  1. 1 Very Strong (PVS1) AND 1 Moderate (PM1–PM6) OR

  2. 1 Strong (PS1–PS4) AND 1–2 Moderate (PM1–PM6) OR

  3. 1 Strong (PS1–PS4) AND ≥2 Supporting (PP1–PP5) OR

  4. ≥3 Moderate (PM1–PM6) OR

  5. 2 Moderate (PM1–PM6) AND ≥2 Supporting (PP1–PP5) OR

  6. 1 Moderate (PM1–PM6) AND ≥4 Supporting (PP1–PP5)

Benign

  1. 1 Stand-Alone (BA1) OR

  2. ≥2 Strong (BS1–BS4)

Likely Benign

  1. 1 Strong (BS1–BS4) and 1 Supporting (BP1–BP7) OR

  2. ≥2 Supporting (BP1–BP7)

*

Variants should be classified as Uncertain Significance if other criteria are unmet or the criteria for benign and pathogenic are contradictory.