TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26004	78235;78236;78237	chr2:178568122;178568121;178568120	chr2:179432849;179432848;179432847
N2AB	24363	73312;73313;73314	chr2:178568122;178568121;178568120	chr2:179432849;179432848;179432847
N2A	23436	70531;70532;70533	chr2:178568122;178568121;178568120	chr2:179432849;179432848;179432847
N2B	16939	51040;51041;51042	chr2:178568122;178568121;178568120	chr2:179432849;179432848;179432847
Novex-1	17064	51415;51416;51417	chr2:178568122;178568121;178568120	chr2:179432849;179432848;179432847
Novex-2	17131	51616;51617;51618	chr2:178568122;178568121;178568120	chr2:179432849;179432848;179432847
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-77
• Domain position: 15
• Structural Position: 17
• Q(SASA): 0.4117
• 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	rs770885887	-0.106	0.999	N	0.589	0.27	0.327419511103	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
K/E	rs770885887	-0.106	0.999	N	0.589	0.27	0.327419511103	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.5604	ambiguous	0.5637	ambiguous	-0.282	Destabilizing	0.999	D	0.633	neutral	None	None	None	None	N
K/C	0.7849	likely_pathogenic	0.7349	pathogenic	-0.385	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
K/D	0.8841	likely_pathogenic	0.8972	pathogenic	-0.529	Destabilizing	1.0	D	0.71	prob.delet.	None	None	None	None	N
K/E	0.4519	ambiguous	0.5	ambiguous	-0.516	Destabilizing	0.999	D	0.589	neutral	N	0.462224071	None	None	N
K/F	0.9441	likely_pathogenic	0.9496	pathogenic	-0.64	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
K/G	0.5967	likely_pathogenic	0.6026	pathogenic	-0.52	Destabilizing	1.0	D	0.68	prob.neutral	None	None	None	None	N
K/H	0.4865	ambiguous	0.4706	ambiguous	-1.077	Destabilizing	1.0	D	0.607	neutral	None	None	None	None	N
K/I	0.7731	likely_pathogenic	0.8025	pathogenic	0.279	Stabilizing	1.0	D	0.709	prob.delet.	N	0.511629446	None	None	N
K/L	0.7298	likely_pathogenic	0.7462	pathogenic	0.279	Stabilizing	1.0	D	0.68	prob.neutral	None	None	None	None	N
K/M	0.5608	ambiguous	0.571	pathogenic	0.497	Stabilizing	1.0	D	0.603	neutral	None	None	None	None	N
K/N	0.7505	likely_pathogenic	0.7604	pathogenic	-0.143	Destabilizing	1.0	D	0.735	prob.delet.	N	0.507589804	None	None	N
K/P	0.8887	likely_pathogenic	0.9141	pathogenic	0.12	Stabilizing	1.0	D	0.669	neutral	None	None	None	None	N
K/Q	0.2558	likely_benign	0.2581	benign	-0.482	Destabilizing	1.0	D	0.727	prob.delet.	N	0.47967367	None	None	N
K/R	0.0739	likely_benign	0.0702	benign	-0.195	Destabilizing	0.999	D	0.533	neutral	N	0.482424788	None	None	N
K/S	0.6459	likely_pathogenic	0.6408	pathogenic	-0.653	Destabilizing	0.999	D	0.678	prob.neutral	None	None	None	None	N
K/T	0.4975	ambiguous	0.5463	ambiguous	-0.485	Destabilizing	1.0	D	0.699	prob.neutral	N	0.472379062	None	None	N
K/V	0.6966	likely_pathogenic	0.721	pathogenic	0.12	Stabilizing	1.0	D	0.694	prob.neutral	None	None	None	None	N
K/W	0.9097	likely_pathogenic	0.9093	pathogenic	-0.576	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
K/Y	0.8672	likely_pathogenic	0.8691	pathogenic	-0.166	Destabilizing	1.0	D	0.692	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.