TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8091	24496;24497;24498	chr2:178718929;178718928;178718927	chr2:179583656;179583655;179583654
N2AB	7774	23545;23546;23547	chr2:178718929;178718928;178718927	chr2:179583656;179583655;179583654
N2A	6847	20764;20765;20766	chr2:178718929;178718928;178718927	chr2:179583656;179583655;179583654
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-66
• Domain position: 14
• Structural Position: 23
• Q(SASA): 0.4041
• Predicted PPI site: I

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/A	None	None	0.767	N	0.415	0.199	0.132336055621	gnomAD-4.0.0	2.05539E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.70058E-06	0	0
P/L	rs1418085481	None	0.999	N	0.724	0.377	0.456647468687	gnomAD-4.0.0	1.59558E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86475E-06	0	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	0.1652	likely_benign	0.1365	benign	-1.348	Destabilizing	0.767	D	0.415	neutral	N	0.476503601	None	None	I
P/C	0.8035	likely_pathogenic	0.7321	pathogenic	-0.84	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	I
P/D	0.8035	likely_pathogenic	0.7675	pathogenic	-1.296	Destabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	I
P/E	0.4912	ambiguous	0.4265	ambiguous	-1.328	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	I
P/F	0.8531	likely_pathogenic	0.81	pathogenic	-1.106	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	I
P/G	0.6314	likely_pathogenic	0.5829	pathogenic	-1.628	Destabilizing	0.997	D	0.649	neutral	None	None	None	None	I
P/H	0.4724	ambiguous	0.4066	ambiguous	-1.165	Destabilizing	1.0	D	0.755	deleterious	N	0.480201924	None	None	I
P/I	0.5953	likely_pathogenic	0.5393	ambiguous	-0.692	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	I
P/K	0.5774	likely_pathogenic	0.5113	ambiguous	-1.269	Destabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	I
P/L	0.2701	likely_benign	0.2213	benign	-0.692	Destabilizing	0.999	D	0.724	prob.delet.	N	0.497302948	None	None	I
P/M	0.6407	likely_pathogenic	0.5719	pathogenic	-0.474	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	I
P/N	0.7028	likely_pathogenic	0.6467	pathogenic	-0.992	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	I
P/Q	0.3594	ambiguous	0.2915	benign	-1.201	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	I
P/R	0.3705	ambiguous	0.3183	benign	-0.661	Destabilizing	0.999	D	0.778	deleterious	N	0.45268992	None	None	I
P/S	0.281	likely_benign	0.2353	benign	-1.433	Destabilizing	0.998	D	0.675	prob.neutral	N	0.479930696	None	None	I
P/T	0.2309	likely_benign	0.1919	benign	-1.364	Destabilizing	0.999	D	0.683	prob.neutral	N	0.478410543	None	None	I
P/V	0.417	ambiguous	0.3694	ambiguous	-0.876	Destabilizing	0.999	D	0.67	neutral	None	None	None	None	I
P/W	0.8801	likely_pathogenic	0.8464	pathogenic	-1.279	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	I
P/Y	0.7948	likely_pathogenic	0.7383	pathogenic	-1.014	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	I

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.