TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2104	6535;6536;6537	chr2:178775554;178775553;178775552	chr2:179640281;179640280;179640279
N2AB	2104	6535;6536;6537	chr2:178775554;178775553;178775552	chr2:179640281;179640280;179640279
N2A	2104	6535;6536;6537	chr2:178775554;178775553;178775552	chr2:179640281;179640280;179640279
N2B	2058	6397;6398;6399	chr2:178775554;178775553;178775552	chr2:179640281;179640280;179640279
Novex-1	2058	6397;6398;6399	chr2:178775554;178775553;178775552	chr2:179640281;179640280;179640279
Novex-2	2058	6397;6398;6399	chr2:178775554;178775553;178775552	chr2:179640281;179640280;179640279
Novex-3	2104	6535;6536;6537	chr2:178775554;178775553;178775552	chr2:179640281;179640280;179640279

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-10
• Domain position: 27
• Structural Position: 41
• Q(SASA): 0.329
• 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	None	None	0.477	N	0.593	0.216	0.241078983079	gnomAD-4.0.0	1.36822E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79862E-06	0	0
K/R	None	None	0.006	N	0.373	0.072	0.206339911435	gnomAD-4.0.0	1.36822E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79862E-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	0.8037	likely_pathogenic	0.7656	pathogenic	0.092	Stabilizing	0.707	D	0.619	neutral	None	None	None	None	I
K/C	0.8872	likely_pathogenic	0.8521	pathogenic	-0.226	Destabilizing	0.995	D	0.736	prob.delet.	None	None	None	None	I
K/D	0.9044	likely_pathogenic	0.8856	pathogenic	-0.194	Destabilizing	0.894	D	0.631	neutral	None	None	None	None	I
K/E	0.6277	likely_pathogenic	0.5583	ambiguous	-0.203	Destabilizing	0.477	N	0.593	neutral	N	0.476128292	None	None	I
K/F	0.9191	likely_pathogenic	0.9042	pathogenic	-0.196	Destabilizing	0.985	D	0.668	neutral	None	None	None	None	I
K/G	0.8768	likely_pathogenic	0.8601	pathogenic	-0.059	Destabilizing	0.894	D	0.563	neutral	None	None	None	None	I
K/H	0.4585	ambiguous	0.426	ambiguous	-0.205	Destabilizing	0.985	D	0.635	neutral	None	None	None	None	I
K/I	0.6517	likely_pathogenic	0.5973	pathogenic	0.409	Stabilizing	0.928	D	0.666	neutral	N	0.466711686	None	None	I
K/L	0.6948	likely_pathogenic	0.652	pathogenic	0.409	Stabilizing	0.894	D	0.563	neutral	None	None	None	None	I
K/M	0.5679	likely_pathogenic	0.5174	ambiguous	0.057	Stabilizing	0.995	D	0.636	neutral	None	None	None	None	I
K/N	0.7586	likely_pathogenic	0.706	pathogenic	0.239	Stabilizing	0.864	D	0.623	neutral	N	0.437433544	None	None	I
K/P	0.9819	likely_pathogenic	0.9807	pathogenic	0.328	Stabilizing	0.945	D	0.623	neutral	None	None	None	None	I
K/Q	0.3158	likely_benign	0.2756	benign	0.079	Stabilizing	0.864	D	0.622	neutral	N	0.493833537	None	None	I
K/R	0.1159	likely_benign	0.1067	benign	0.02	Stabilizing	0.006	N	0.373	neutral	N	0.479780528	None	None	I
K/S	0.7919	likely_pathogenic	0.7526	pathogenic	-0.136	Destabilizing	0.707	D	0.639	neutral	None	None	None	None	I
K/T	0.522	ambiguous	0.4727	ambiguous	-0.022	Destabilizing	0.864	D	0.59	neutral	N	0.464631586	None	None	I
K/V	0.6371	likely_pathogenic	0.5791	pathogenic	0.328	Stabilizing	0.894	D	0.637	neutral	None	None	None	None	I
K/W	0.9034	likely_pathogenic	0.8937	pathogenic	-0.287	Destabilizing	0.995	D	0.745	deleterious	None	None	None	None	I
K/Y	0.806	likely_pathogenic	0.7747	pathogenic	0.068	Stabilizing	0.945	D	0.659	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.