Novel Synonymous and Deep Intronic Variants Causing Primary and Secondary Pyruvate Dehydrogenase Complex Deficiency

Table 1

Binding site sequences for ESEs and in silico prediction scores of synonymous variants in PDHA1.

Splicing prediction tool	PDHA1 c.447A>G, p.(Lys149=)		PDHA1 c.570C>T, p.(Cys190=)
	WT	Variant	WT	Variant
ESEFinder SRSF1 (SF2/ASF)	2,09 (GAAAGGA)	0	2,21 (CTGCCTG)	0
RESCUE_ESE	1 (AAAGGA)	0	0	0
EX-SKIP (ESS/ESE ratio)	0,22	0,33	0,54	0,67
SpliceAI	NA	Δ0,49 (intron 4 AL)	NA	Δ0,33 (intron 6 DL)

Abbreviations: AL = acceptor site loss; DL = donor site loss; ESE = exonic splicing enhancer; ESS = exonic splicing silencer; NA = not applicable; SRSF1 (SF2/ASF) = alternative splicing factor 2; WT = wild type. The nucleotides changed by the variants are underlined. Reference sequence: RefSeq NM_000284.4.