TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32323	97192;97193;97194	chr2:178542887;178542886;178542885	chr2:179407614;179407613;179407612
N2AB	30682	92269;92270;92271	chr2:178542887;178542886;178542885	chr2:179407614;179407613;179407612
N2A	29755	89488;89489;89490	chr2:178542887;178542886;178542885	chr2:179407614;179407613;179407612
N2B	23258	69997;69998;69999	chr2:178542887;178542886;178542885	chr2:179407614;179407613;179407612
Novex-1	23383	70372;70373;70374	chr2:178542887;178542886;178542885	chr2:179407614;179407613;179407612
Novex-2	23450	70573;70574;70575	chr2:178542887;178542886;178542885	chr2:179407614;179407613;179407612
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: Ig-154
• Domain position: 17
• Structural Position: 26
• Q(SASA): 0.4524
• 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/L	rs1695272344	None	0.999	N	0.781	0.356	0.506311303838	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
P/L	rs1695272344	None	0.999	N	0.781	0.356	0.506311303838	gnomAD-4.0.0	6.57341E-06	None	None	None	None	N	None	0	6.54879E-05	None	0	0	None	0	0	0	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	0.0963	likely_benign	0.0935	benign	-1.441	Destabilizing	0.998	D	0.679	prob.neutral	N	0.473255439	None	None	N
P/C	0.6732	likely_pathogenic	0.6056	pathogenic	-0.975	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
P/D	0.6379	likely_pathogenic	0.5836	pathogenic	-1.31	Destabilizing	0.998	D	0.753	deleterious	None	None	None	None	N
P/E	0.5164	ambiguous	0.4714	ambiguous	-1.347	Destabilizing	0.999	D	0.762	deleterious	None	None	None	None	N
P/F	0.708	likely_pathogenic	0.6388	pathogenic	-1.226	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
P/G	0.3884	ambiguous	0.3783	ambiguous	-1.723	Destabilizing	0.997	D	0.697	prob.neutral	None	None	None	None	N
P/H	0.377	ambiguous	0.3064	benign	-1.237	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
P/I	0.4969	ambiguous	0.449	ambiguous	-0.781	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
P/K	0.5395	ambiguous	0.472	ambiguous	-1.201	Destabilizing	0.999	D	0.751	deleterious	None	None	None	None	N
P/L	0.2235	likely_benign	0.1831	benign	-0.781	Destabilizing	0.999	D	0.781	deleterious	N	0.455945604	None	None	N
P/M	0.4347	ambiguous	0.3857	ambiguous	-0.556	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
P/N	0.4274	ambiguous	0.3871	ambiguous	-0.926	Destabilizing	0.91	D	0.427	neutral	None	None	None	None	N
P/Q	0.3177	likely_benign	0.2835	benign	-1.162	Destabilizing	0.999	D	0.797	deleterious	N	0.488147534	None	None	N
P/R	0.3887	ambiguous	0.3236	benign	-0.613	Destabilizing	0.999	D	0.773	deleterious	N	0.465540033	None	None	N
P/S	0.1837	likely_benign	0.1687	benign	-1.413	Destabilizing	0.999	D	0.738	prob.delet.	N	0.44344982	None	None	N
P/T	0.1545	likely_benign	0.1329	benign	-1.347	Destabilizing	0.999	D	0.762	deleterious	N	0.402949992	None	None	N
P/V	0.3162	likely_benign	0.2921	benign	-0.966	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
P/W	0.839	likely_pathogenic	0.7838	pathogenic	-1.356	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
P/Y	0.6852	likely_pathogenic	0.6081	pathogenic	-1.091	Destabilizing	1.0	D	0.793	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.