Table 2

Workgroup GLA variant phenotype classification consensus results; Stages 1–4

Fabry Registry
GLA variants
(n=33)
Variant typeNo. of males with genotypeNo. of males with genotype and usable clinical data* GLA variant 2-point score (%) GLA variant phenotype consensus†
ProvisionalFinal
Stage 1Stage 2Stages 3 and 4
p.Trp44CysMissense75100ClassicClassicClassic
p.Met284ThrMissense66100Classic‡Classic
c.777delFrameshift65100Classic‡Classic
c.1042dupFrameshift5100Classic‡Classic
p.Ser65_Tyr123delLarge deletion44100Classic‡Classic
c.1212_1214delSmall deletion7100Classic‡Classic
p.Ser345ProMissense111087UnclassifiedClassicClassic
c.370-2A>GSplice site5586Classic‡Classic
c.802–3_802-2delSplice site5483Classic‡Classic
c.57_82delFrameshift4483Classic‡Classic
p.Gln283*Nonsense480ClassicClassicClassic
p.Ala156ThrMissense5480ClassicClassicClassic
p.Thr194IleMissense5580ClassicClassicClassic
c.548–1G>ASplice site4480Classic‡Classic
c.365_371delFrameshift6580Classic‡Classic
p.Glu358delSmall deletion13977ClassicClassicClassic
c.1188_1189insTFrameshift5475ClassicClassicClassic
p.Ala15GluMissense6471Classic‡Classic
p.Trp162*Nonsense7670ClassicClassicClassic
p.Pro259ArgMissense282169ClassicClassicClassic
p.Trp340ArgMissense4467Classic‡Classic
p.Thr410IleMissense5563ClassicClassicClassic
c.568delFrameshift460Classic‡Classic
c.639+4A>TIntronic6460Classic‡Classic
c.1000–10G>AIntronic4460Classic‡Classic
p.Ile198ThrMissense8443Later-onset‡Later-onset
c.999+2T>CSplice site5440Unclassified‡Classic
p.Ser238AsnMissense11836ClassicLater-onsetLater-onset
c.639+919G>AIntronic131031Later-onset‡Later-onset
p.Arg363HisMissense12529Later-onsetLater-onsetLater-onset
p.Asp322GluMissense7627UnclassifiedUnclassifiedLater-onset
p.Ala143ThrMissense241327UnclassifiedUnclassifiedGVUS¶
p.Ile117SerMissense6625Later-onset‡Later-onset
  • *Usable data on angiokeratomas or cornea verticillata status available in the Fabry Registry.

  • †Phenotypes associated with ‘pathogenic’ GLA variants include ‘classic’ and ‘later-onset’ phenotypes.

  • ‡Novel GLA variants (n=19) resulting from using a more recent Fabry Registry reconciled data download (July 2016) added during Stage 2 of the process (hence the 'dash' in the Stage one column).

  • §Null variant present in ≥4 male patients with <4 patients having 2-point scoring data available. Included in the process as the deleterious impact of the variant dominated the expert’s overall clinical phenotype assessment as ‘classic’.

  • ¶Genetic variant of unknown significance; experts’ opinion in favour of a likely benign GLA variant.