TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15340	46243;46244;46245	chr2:178620503;178620502;178620501	chr2:179485230;179485229;179485228
N2AB	13699	41320;41321;41322	chr2:178620503;178620502;178620501	chr2:179485230;179485229;179485228
N2A	12772	38539;38540;38541	chr2:178620503;178620502;178620501	chr2:179485230;179485229;179485228
N2B	6275	19048;19049;19050	chr2:178620503;178620502;178620501	chr2:179485230;179485229;179485228
Novex-1	6400	19423;19424;19425	chr2:178620503;178620502;178620501	chr2:179485230;179485229;179485228
Novex-2	6467	19624;19625;19626	chr2:178620503;178620502;178620501	chr2:179485230;179485229;179485228
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-105
• Domain position: 39
• Structural Position: 56
• Q(SASA): 0.4688
• 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
E/D	rs1576546728	None	0.979	D	0.469	0.287	0.415820034956	gnomAD-4.0.0	1.36953E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80008E-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
E/A	0.1706	likely_benign	0.1236	benign	-0.431	Destabilizing	0.958	D	0.589	neutral	D	0.606721742	None	None	N
E/C	0.8797	likely_pathogenic	0.8617	pathogenic	-0.221	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
E/D	0.1455	likely_benign	0.1174	benign	-0.48	Destabilizing	0.979	D	0.469	neutral	D	0.644988015	None	None	N
E/F	0.7244	likely_pathogenic	0.6626	pathogenic	-0.167	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
E/G	0.2851	likely_benign	0.1951	benign	-0.662	Destabilizing	0.988	D	0.627	neutral	D	0.689304282	None	None	N
E/H	0.572	likely_pathogenic	0.5096	ambiguous	0.026	Stabilizing	0.999	D	0.601	neutral	None	None	None	None	N
E/I	0.2941	likely_benign	0.2402	benign	0.154	Stabilizing	0.995	D	0.731	prob.delet.	None	None	None	None	N
E/K	0.2183	likely_benign	0.1542	benign	0.115	Stabilizing	0.919	D	0.493	neutral	D	0.590826421	None	None	N
E/L	0.4098	ambiguous	0.329	benign	0.154	Stabilizing	0.991	D	0.698	prob.neutral	None	None	None	None	N
E/M	0.4442	ambiguous	0.3662	ambiguous	0.191	Stabilizing	1.0	D	0.667	neutral	None	None	None	None	N
E/N	0.2773	likely_benign	0.2144	benign	-0.287	Destabilizing	0.991	D	0.609	neutral	None	None	None	None	N
E/P	0.3891	ambiguous	0.3486	ambiguous	-0.02	Destabilizing	0.998	D	0.697	prob.neutral	None	None	None	None	N
E/Q	0.2348	likely_benign	0.178	benign	-0.218	Destabilizing	0.958	D	0.554	neutral	D	0.606297485	None	None	N
E/R	0.3585	ambiguous	0.2883	benign	0.389	Stabilizing	0.18	N	0.25	neutral	None	None	None	None	N
E/S	0.2575	likely_benign	0.1869	benign	-0.444	Destabilizing	0.968	D	0.578	neutral	None	None	None	None	N
E/T	0.2323	likely_benign	0.1779	benign	-0.254	Destabilizing	0.991	D	0.662	neutral	None	None	None	None	N
E/V	0.1867	likely_benign	0.1485	benign	-0.02	Destabilizing	0.994	D	0.707	prob.neutral	D	0.575153155	None	None	N
E/W	0.9054	likely_pathogenic	0.8789	pathogenic	0.015	Stabilizing	1.0	D	0.706	prob.neutral	None	None	None	None	N
E/Y	0.6297	likely_pathogenic	0.5665	pathogenic	0.073	Stabilizing	0.998	D	0.695	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.