Clinical, biochemical, and genetic analysis of 28 Chinese patients with holocarboxylase synthetase deficiency

Table 3 Prediction of the potential pathogenic effect of novel missense variants of HLCS gene

Mutation	Domain	PROVEAN^a	PolyPhen-2^b	SIFT^c	Mutation taster^d	Conservation
I686S	C-terminal of BPL	Deleterious	Probably damaging	Damaging	142	Conserved
P609S	catalytic domain	Deleterious	Probably damaging	Damaging	74	Conserved
G466V	catalytic domain	Deleterious	Probably damaging	Damaging	109	Conserved
T478M	catalytic domain	Deleterious	Probably damaging	Damaging	81	Conserved
G494V	catalytic domain	Deleterious	Probably damaging	Damaging	109	Conserved

Biotin protein ligase, (BPL)
^aPROVEAN prediction: default threshold is − 2.5, that is variants with a score equal to or below − 2.5 are considered “deleterious”, whereas variants with a score above − 2.5 are considered “neutral”
^bPolyPhen-2 prediction: probably damaging with a score above 0.909, in contrast, possibly damaging with a score between 0.447 and 0.908, benign with a score under 0.446
^cSIFT prediction: amino acids with probabilities < 0.05 are predicted to be deleterious, whereas variants with a score above 0.05 are considered “neutral”
^dMutation taster prediction: scores range from 0.0 to 215. The more they score, the more deleterious protein mutations

ISSN: 1750-1172