TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29086	87481;87482;87483	chr2:178558098;178558097;178558096	chr2:179422825;179422824;179422823
N2AB	27445	82558;82559;82560	chr2:178558098;178558097;178558096	chr2:179422825;179422824;179422823
N2A	26518	79777;79778;79779	chr2:178558098;178558097;178558096	chr2:179422825;179422824;179422823
N2B	20021	60286;60287;60288	chr2:178558098;178558097;178558096	chr2:179422825;179422824;179422823
Novex-1	20146	60661;60662;60663	chr2:178558098;178558097;178558096	chr2:179422825;179422824;179422823
Novex-2	20213	60862;60863;60864	chr2:178558098;178558097;178558096	chr2:179422825;179422824;179422823
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-145
• Domain position: 42
• Structural Position: 59
• Q(SASA): 0.7447
• 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
K/E	None	None	0.928	N	0.581	0.396	0.36036328697	gnomAD-4.0.0	1.59103E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85781E-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
K/A	0.5431	ambiguous	0.5313	ambiguous	-0.036	Destabilizing	0.944	D	0.624	neutral	None	None	None	None	N
K/C	0.8236	likely_pathogenic	0.8051	pathogenic	-0.523	Destabilizing	0.999	D	0.721	prob.delet.	None	None	None	None	N
K/D	0.8355	likely_pathogenic	0.83	pathogenic	-0.401	Destabilizing	0.992	D	0.685	prob.neutral	None	None	None	None	N
K/E	0.4517	ambiguous	0.4261	ambiguous	-0.423	Destabilizing	0.928	D	0.581	neutral	N	0.514415068	None	None	N
K/F	0.8862	likely_pathogenic	0.877	pathogenic	-0.421	Destabilizing	0.999	D	0.704	prob.neutral	None	None	None	None	N
K/G	0.687	likely_pathogenic	0.6753	pathogenic	-0.135	Destabilizing	0.983	D	0.585	neutral	None	None	None	None	N
K/H	0.4167	ambiguous	0.3882	ambiguous	-0.211	Destabilizing	0.998	D	0.671	neutral	None	None	None	None	N
K/I	0.556	ambiguous	0.5505	ambiguous	0.141	Stabilizing	0.992	D	0.715	prob.delet.	None	None	None	None	N
K/L	0.5027	ambiguous	0.4999	ambiguous	0.141	Stabilizing	0.983	D	0.585	neutral	None	None	None	None	N
K/M	0.4163	ambiguous	0.4145	ambiguous	-0.211	Destabilizing	0.999	D	0.668	neutral	D	0.527539081	None	None	N
K/N	0.7163	likely_pathogenic	0.716	pathogenic	-0.077	Destabilizing	0.978	D	0.645	neutral	D	0.532750113	None	None	N
K/P	0.664	likely_pathogenic	0.649	pathogenic	0.103	Stabilizing	0.997	D	0.669	neutral	None	None	None	None	N
K/Q	0.2173	likely_benign	0.1992	benign	-0.214	Destabilizing	0.978	D	0.633	neutral	N	0.514761785	None	None	N
K/R	0.0873	likely_benign	0.0859	benign	-0.2	Destabilizing	0.085	N	0.317	neutral	N	0.463236886	None	None	N
K/S	0.6862	likely_pathogenic	0.6843	pathogenic	-0.405	Destabilizing	0.944	D	0.589	neutral	None	None	None	None	N
K/T	0.3649	ambiguous	0.3612	ambiguous	-0.326	Destabilizing	0.978	D	0.635	neutral	N	0.488364617	None	None	N
K/V	0.4937	ambiguous	0.4911	ambiguous	0.103	Stabilizing	0.992	D	0.688	prob.neutral	None	None	None	None	N
K/W	0.8697	likely_pathogenic	0.8399	pathogenic	-0.545	Destabilizing	0.999	D	0.729	prob.delet.	None	None	None	None	N
K/Y	0.7924	likely_pathogenic	0.7689	pathogenic	-0.203	Destabilizing	0.997	D	0.686	prob.neutral	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.