TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21851	65776;65777;65778	chr2:178583631;178583630;178583629	chr2:179448358;179448357;179448356
N2AB	20210	60853;60854;60855	chr2:178583631;178583630;178583629	chr2:179448358;179448357;179448356
N2A	19283	58072;58073;58074	chr2:178583631;178583630;178583629	chr2:179448358;179448357;179448356
N2B	12786	38581;38582;38583	chr2:178583631;178583630;178583629	chr2:179448358;179448357;179448356
Novex-1	12911	38956;38957;38958	chr2:178583631;178583630;178583629	chr2:179448358;179448357;179448356
Novex-2	12978	39157;39158;39159	chr2:178583631;178583630;178583629	chr2:179448358;179448357;179448356
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-46
• Domain position: 95
• Structural Position: 126
• Q(SASA): 0.2094
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
P/T	None	None	0.953	N	0.637	0.249	0.298745278005	gnomAD-4.0.0	6.86624E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.16844E-05	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
P/A	0.0732	likely_benign	0.0595	benign	-0.702	Destabilizing	0.214	N	0.454	neutral	N	0.465409534	None	None	N
P/C	0.5278	ambiguous	0.3899	ambiguous	-0.69	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
P/D	0.5419	ambiguous	0.4798	ambiguous	-0.353	Destabilizing	0.995	D	0.605	neutral	None	None	None	None	N
P/E	0.3507	ambiguous	0.3094	benign	-0.441	Destabilizing	0.995	D	0.603	neutral	None	None	None	None	N
P/F	0.5619	ambiguous	0.43	ambiguous	-0.733	Destabilizing	0.995	D	0.75	deleterious	None	None	None	None	N
P/G	0.4067	ambiguous	0.343	ambiguous	-0.892	Destabilizing	0.964	D	0.681	prob.neutral	None	None	None	None	N
P/H	0.2948	likely_benign	0.2267	benign	-0.367	Destabilizing	1.0	D	0.694	prob.delet.	None	None	None	None	N
P/I	0.2816	likely_benign	0.2073	benign	-0.338	Destabilizing	0.979	D	0.685	prob.delet.	None	None	None	None	N
P/K	0.3683	ambiguous	0.3143	benign	-0.593	Destabilizing	0.995	D	0.595	neutral	None	None	None	None	N
P/L	0.1499	likely_benign	0.117	benign	-0.338	Destabilizing	0.91	D	0.727	deleterious	N	0.512856764	None	None	N
P/M	0.3454	ambiguous	0.2627	benign	-0.352	Destabilizing	0.999	D	0.697	prob.delet.	None	None	None	None	N
P/N	0.4269	ambiguous	0.3576	ambiguous	-0.331	Destabilizing	0.998	D	0.695	prob.delet.	None	None	None	None	N
P/Q	0.2512	likely_benign	0.1982	benign	-0.564	Destabilizing	0.998	D	0.571	neutral	N	0.480351098	None	None	N
P/R	0.2302	likely_benign	0.1954	benign	-0.047	Destabilizing	0.993	D	0.696	prob.delet.	N	0.469248282	None	None	N
P/S	0.157	likely_benign	0.1293	benign	-0.769	Destabilizing	0.91	D	0.637	neutral	N	0.502333126	None	None	N
P/T	0.1039	likely_benign	0.0866	benign	-0.749	Destabilizing	0.953	D	0.637	neutral	N	0.51805194	None	None	N
P/V	0.178	likely_benign	0.1372	benign	-0.423	Destabilizing	0.455	N	0.628	neutral	None	None	None	None	N
P/W	0.7737	likely_pathogenic	0.6799	pathogenic	-0.814	Destabilizing	1.0	D	0.696	prob.delet.	None	None	None	None	N
P/Y	0.5589	ambiguous	0.4276	ambiguous	-0.521	Destabilizing	0.998	D	0.751	deleterious	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.