TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17077	51454;51455;51456	chr2:178610297;178610296;178610295	chr2:179475024;179475023;179475022
N2AB	15436	46531;46532;46533	chr2:178610297;178610296;178610295	chr2:179475024;179475023;179475022
N2A	14509	43750;43751;43752	chr2:178610297;178610296;178610295	chr2:179475024;179475023;179475022
N2B	8012	24259;24260;24261	chr2:178610297;178610296;178610295	chr2:179475024;179475023;179475022
Novex-1	8137	24634;24635;24636	chr2:178610297;178610296;178610295	chr2:179475024;179475023;179475022
Novex-2	8204	24835;24836;24837	chr2:178610297;178610296;178610295	chr2:179475024;179475023;179475022
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-12
• Domain position: 31
• Structural Position: 33
• Q(SASA): 0.2576
• 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
T/I	None	None	0.117	N	0.629	0.081	0.215109475489	gnomAD-4.0.0	1.20033E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.31252E-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
T/A	0.1165	likely_benign	0.1146	benign	-0.819	Destabilizing	0.012	N	0.442	neutral	N	0.406974058	None	None	I
T/C	0.3735	ambiguous	0.401	ambiguous	-0.536	Destabilizing	0.824	D	0.633	neutral	None	None	None	None	I
T/D	0.61	likely_pathogenic	0.5938	pathogenic	-0.468	Destabilizing	0.081	N	0.572	neutral	None	None	None	None	I
T/E	0.6281	likely_pathogenic	0.5576	ambiguous	-0.455	Destabilizing	0.081	N	0.571	neutral	None	None	None	None	I
T/F	0.4312	ambiguous	0.4549	ambiguous	-0.824	Destabilizing	0.555	D	0.68	prob.neutral	None	None	None	None	I
T/G	0.3665	ambiguous	0.3856	ambiguous	-1.094	Destabilizing	0.035	N	0.609	neutral	None	None	None	None	I
T/H	0.4282	ambiguous	0.4343	ambiguous	-1.392	Destabilizing	0.555	D	0.674	neutral	None	None	None	None	I
T/I	0.4798	ambiguous	0.4718	ambiguous	-0.17	Destabilizing	0.117	N	0.629	neutral	N	0.473315917	None	None	I
T/K	0.6874	likely_pathogenic	0.6428	pathogenic	-0.814	Destabilizing	0.081	N	0.569	neutral	None	None	None	None	I
T/L	0.2	likely_benign	0.1873	benign	-0.17	Destabilizing	0.149	N	0.578	neutral	None	None	None	None	I
T/M	0.1212	likely_benign	0.1123	benign	0.151	Stabilizing	0.791	D	0.637	neutral	None	None	None	None	I
T/N	0.2124	likely_benign	0.2197	benign	-0.808	Destabilizing	0.062	N	0.561	neutral	N	0.475467915	None	None	I
T/P	0.8657	likely_pathogenic	0.8695	pathogenic	-0.354	Destabilizing	0.117	N	0.631	neutral	N	0.478053442	None	None	I
T/Q	0.4879	ambiguous	0.4508	ambiguous	-0.973	Destabilizing	0.38	N	0.649	neutral	None	None	None	None	I
T/R	0.6566	likely_pathogenic	0.6141	pathogenic	-0.591	Destabilizing	0.38	N	0.635	neutral	None	None	None	None	I
T/S	0.0892	likely_benign	0.0989	benign	-1.066	Destabilizing	None	N	0.275	neutral	N	0.31529521	None	None	I
T/V	0.3342	likely_benign	0.3234	benign	-0.354	Destabilizing	0.149	N	0.564	neutral	None	None	None	None	I
T/W	0.7743	likely_pathogenic	0.8199	pathogenic	-0.768	Destabilizing	0.935	D	0.685	prob.neutral	None	None	None	None	I
T/Y	0.4016	ambiguous	0.4501	ambiguous	-0.534	Destabilizing	0.555	D	0.685	prob.neutral	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.