TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22447	67564;67565;67566	chr2:178579948;178579947;178579946	chr2:179444675;179444674;179444673
N2AB	20806	62641;62642;62643	chr2:178579948;178579947;178579946	chr2:179444675;179444674;179444673
N2A	19879	59860;59861;59862	chr2:178579948;178579947;178579946	chr2:179444675;179444674;179444673
N2B	13382	40369;40370;40371	chr2:178579948;178579947;178579946	chr2:179444675;179444674;179444673
Novex-1	13507	40744;40745;40746	chr2:178579948;178579947;178579946	chr2:179444675;179444674;179444673
Novex-2	13574	40945;40946;40947	chr2:178579948;178579947;178579946	chr2:179444675;179444674;179444673
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: Fn3-50
• Domain position: 94
• Structural Position: 129
• Q(SASA): 0.5039
• 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/R	rs766331736	0.343	0.029	N	0.197	0.093	0.250039746154	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.93E-06	0
K/R	rs766331736	0.343	0.029	N	0.197	0.093	0.250039746154	gnomAD-4.0.0	4.77812E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86049E-06	0	6.05437E-05

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	0.7449	likely_pathogenic	0.6826	pathogenic	-0.161	Destabilizing	0.984	D	0.587	neutral	None	None	None	None	N
K/C	0.8836	likely_pathogenic	0.8268	pathogenic	-0.356	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
K/D	0.9535	likely_pathogenic	0.9373	pathogenic	0.49	Stabilizing	0.995	D	0.608	neutral	None	None	None	None	N
K/E	0.6199	likely_pathogenic	0.5595	ambiguous	0.508	Stabilizing	0.958	D	0.556	neutral	N	0.481208493	None	None	N
K/F	0.9234	likely_pathogenic	0.8993	pathogenic	-0.414	Destabilizing	0.998	D	0.815	deleterious	None	None	None	None	N
K/G	0.9048	likely_pathogenic	0.8694	pathogenic	-0.358	Destabilizing	0.984	D	0.603	neutral	None	None	None	None	N
K/H	0.6207	likely_pathogenic	0.5354	ambiguous	-0.676	Destabilizing	0.998	D	0.719	prob.delet.	None	None	None	None	N
K/I	0.5117	ambiguous	0.4686	ambiguous	0.279	Stabilizing	0.998	D	0.809	deleterious	N	0.475743958	None	None	N
K/L	0.5613	ambiguous	0.5157	ambiguous	0.279	Stabilizing	0.984	D	0.603	neutral	None	None	None	None	N
K/M	0.4385	ambiguous	0.3963	ambiguous	0.17	Stabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
K/N	0.8714	likely_pathogenic	0.8411	pathogenic	0.23	Stabilizing	0.994	D	0.571	neutral	N	0.461766317	None	None	N
K/P	0.9059	likely_pathogenic	0.878	pathogenic	0.16	Stabilizing	0.998	D	0.699	prob.delet.	None	None	None	None	N
K/Q	0.3469	ambiguous	0.2933	benign	0.057	Stabilizing	0.988	D	0.6	neutral	N	0.498890176	None	None	N
K/R	0.0962	likely_benign	0.0882	benign	0.012	Stabilizing	0.029	N	0.197	neutral	N	0.437399001	None	None	N
K/S	0.8712	likely_pathogenic	0.8286	pathogenic	-0.4	Destabilizing	0.984	D	0.527	neutral	None	None	None	None	N
K/T	0.4033	ambiguous	0.3503	ambiguous	-0.22	Destabilizing	0.979	D	0.644	neutral	N	0.412910696	None	None	N
K/V	0.4854	ambiguous	0.4342	ambiguous	0.16	Stabilizing	0.995	D	0.593	neutral	None	None	None	None	N
K/W	0.923	likely_pathogenic	0.8918	pathogenic	-0.365	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
K/Y	0.8714	likely_pathogenic	0.8306	pathogenic	None	Stabilizing	0.998	D	0.84	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.