Table 1.

Pathogenic variants in the OTULIN gene of ORAS patients

CDS positionAA alterationSoftware predictionReference
SIFTPolyPhen-2CADDMutation Taster
Maternal allele c.455C>T p.P152L 0.21 0.002 21 Benign This paper 
de novo c.917G>A p.R306Q 0.999 32 Deleterious This paper 
ORAS c.815T>C p.L272P 0.03 0.999 29.2 Deleterious Damgaard et al., 2016; Zhou et al., 2016  
ORAS c.731A>G p.Y244C 0.925 26.6 Deleterious Zhou et al., 2016  
ORAS c.841G>A p.G281R 0.999 31 Deleterious Damgaard et al., 2019  
Atypical ORAS c.258G>A p.M86I 0.5 0.191 23.2 Zinngrebe et al., 2022  
Atypical ORAS c.500G>C p.W167S 31 Deleterious Zinngrebe et al., 2022  
CDS positionAA alterationSoftware predictionReference
SIFTPolyPhen-2CADDMutation Taster
Maternal allele c.455C>T p.P152L 0.21 0.002 21 Benign This paper 
de novo c.917G>A p.R306Q 0.999 32 Deleterious This paper 
ORAS c.815T>C p.L272P 0.03 0.999 29.2 Deleterious Damgaard et al., 2016; Zhou et al., 2016  
ORAS c.731A>G p.Y244C 0.925 26.6 Deleterious Zhou et al., 2016  
ORAS c.841G>A p.G281R 0.999 31 Deleterious Damgaard et al., 2019  
Atypical ORAS c.258G>A p.M86I 0.5 0.191 23.2 Zinngrebe et al., 2022  
Atypical ORAS c.500G>C p.W167S 31 Deleterious Zinngrebe et al., 2022  

CDS, coding sequence; AA, amino acid; SIFT, Sorting Intolerant From Tolerant (<0.05 = deleterious); PolyPhen-2, Polymorphism Phenotyping v2 (>0.85 is “probably damaging” and <0.15 is “benign”); CADD, Combined Annotation Dependent Depletion (raw values have relative meaning, with higher values indicating a higher likelihood of deleterious effects).

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