TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18669	56230;56231;56232	chr2:178600899;178600898;178600897	chr2:179465626;179465625;179465624
N2AB	17028	51307;51308;51309	chr2:178600899;178600898;178600897	chr2:179465626;179465625;179465624
N2A	16101	48526;48527;48528	chr2:178600899;178600898;178600897	chr2:179465626;179465625;179465624
N2B	9604	29035;29036;29037	chr2:178600899;178600898;178600897	chr2:179465626;179465625;179465624
Novex-1	9729	29410;29411;29412	chr2:178600899;178600898;178600897	chr2:179465626;179465625;179465624
Novex-2	9796	29611;29612;29613	chr2:178600899;178600898;178600897	chr2:179465626;179465625;179465624
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: Fn3-23
• Domain position: 91
• Structural Position: 119
• Q(SASA): 0.6799
• 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
K/E	rs749362468	0.2	0.334	N	0.534	0.17	0.201204373187	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
K/E	rs749362468	0.2	0.334	N	0.534	0.17	0.201204373187	gnomAD-4.0.0	1.36911E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	2.31986E-05	0
K/N	None	None	0.549	N	0.565	0.133	0.0954503805726	gnomAD-4.0.0	1.59328E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	2.41896E-04	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
K/A	0.4991	ambiguous	0.4278	ambiguous	-0.025	Destabilizing	0.4	N	0.501	neutral	None	None	None	None	I
K/C	0.8415	likely_pathogenic	0.7412	pathogenic	-0.228	Destabilizing	0.992	D	0.603	neutral	None	None	None	None	I
K/D	0.7422	likely_pathogenic	0.7075	pathogenic	-0.047	Destabilizing	0.617	D	0.592	neutral	None	None	None	None	I
K/E	0.3494	ambiguous	0.3273	benign	-0.022	Destabilizing	0.334	N	0.534	neutral	N	0.389455912	None	None	I
K/F	0.8565	likely_pathogenic	0.8053	pathogenic	-0.136	Destabilizing	0.972	D	0.579	neutral	None	None	None	None	I
K/G	0.6445	likely_pathogenic	0.5387	ambiguous	-0.248	Destabilizing	0.617	D	0.573	neutral	None	None	None	None	I
K/H	0.4679	ambiguous	0.3665	ambiguous	-0.475	Destabilizing	0.92	D	0.579	neutral	None	None	None	None	I
K/I	0.4852	ambiguous	0.4485	ambiguous	0.491	Stabilizing	0.92	D	0.576	neutral	None	None	None	None	I
K/L	0.4328	ambiguous	0.3714	ambiguous	0.491	Stabilizing	0.617	D	0.573	neutral	None	None	None	None	I
K/M	0.3887	ambiguous	0.3712	ambiguous	0.147	Stabilizing	0.963	D	0.573	neutral	N	0.477731044	None	None	I
K/N	0.6096	likely_pathogenic	0.5735	pathogenic	0.121	Stabilizing	0.549	D	0.565	neutral	N	0.462300232	None	None	I
K/P	0.6124	likely_pathogenic	0.513	ambiguous	0.347	Stabilizing	0.92	D	0.605	neutral	None	None	None	None	I
K/Q	0.2193	likely_benign	0.1775	benign	-0.002	Destabilizing	0.549	D	0.614	neutral	N	0.429014378	None	None	I
K/R	0.0921	likely_benign	0.0705	benign	-0.111	Destabilizing	0.001	N	0.114	neutral	N	0.394267086	None	None	I
K/S	0.6006	likely_pathogenic	0.5465	ambiguous	-0.321	Destabilizing	0.617	D	0.508	neutral	None	None	None	None	I
K/T	0.3559	ambiguous	0.3302	benign	-0.142	Destabilizing	0.549	D	0.562	neutral	N	0.460241362	None	None	I
K/V	0.4498	ambiguous	0.4082	ambiguous	0.347	Stabilizing	0.85	D	0.567	neutral	None	None	None	None	I
K/W	0.8555	likely_pathogenic	0.7524	pathogenic	-0.17	Destabilizing	0.992	D	0.677	prob.neutral	None	None	None	None	I
K/Y	0.7301	likely_pathogenic	0.6723	pathogenic	0.166	Stabilizing	0.972	D	0.571	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.