TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24113	72562;72563;72564	chr2:178573795;178573794;178573793	chr2:179438522;179438521;179438520
N2AB	22472	67639;67640;67641	chr2:178573795;178573794;178573793	chr2:179438522;179438521;179438520
N2A	21545	64858;64859;64860	chr2:178573795;178573794;178573793	chr2:179438522;179438521;179438520
N2B	15048	45367;45368;45369	chr2:178573795;178573794;178573793	chr2:179438522;179438521;179438520
Novex-1	15173	45742;45743;45744	chr2:178573795;178573794;178573793	chr2:179438522;179438521;179438520
Novex-2	15240	45943;45944;45945	chr2:178573795;178573794;178573793	chr2:179438522;179438521;179438520
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Ig-131
• Domain position: 85
• Structural Position: 169
• Q(SASA): 0.2467
• 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
H/P	None	None	0.996	N	0.673	0.422	0.503930629158	gnomAD-4.0.0	3.19953E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.746E-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
H/A	0.3215	likely_benign	0.39	ambiguous	-1.478	Destabilizing	0.969	D	0.606	neutral	None	None	None	None	N
H/C	0.1525	likely_benign	0.1874	benign	-0.799	Destabilizing	0.999	D	0.679	prob.neutral	None	None	None	None	N
H/D	0.5106	ambiguous	0.5892	pathogenic	-1.426	Destabilizing	0.986	D	0.623	neutral	N	0.498656182	None	None	N
H/E	0.3615	ambiguous	0.4382	ambiguous	-1.255	Destabilizing	0.99	D	0.583	neutral	None	None	None	None	N
H/F	0.2338	likely_benign	0.2618	benign	0.246	Stabilizing	0.02	N	0.313	neutral	None	None	None	None	N
H/G	0.5476	ambiguous	0.5875	pathogenic	-1.886	Destabilizing	0.99	D	0.627	neutral	None	None	None	None	N
H/I	0.2755	likely_benign	0.3533	ambiguous	-0.295	Destabilizing	0.939	D	0.691	prob.neutral	None	None	None	None	N
H/K	0.376	ambiguous	0.4332	ambiguous	-0.99	Destabilizing	0.99	D	0.619	neutral	None	None	None	None	N
H/L	0.1754	likely_benign	0.2072	benign	-0.295	Destabilizing	0.852	D	0.636	neutral	N	0.449094153	None	None	N
H/M	0.4414	ambiguous	0.502	ambiguous	-0.561	Destabilizing	0.997	D	0.653	neutral	None	None	None	None	N
H/N	0.1756	likely_benign	0.2194	benign	-1.695	Destabilizing	0.986	D	0.623	neutral	N	0.520647607	None	None	N
H/P	0.8865	likely_pathogenic	0.8806	pathogenic	-0.676	Destabilizing	0.996	D	0.673	neutral	N	0.495821321	None	None	N
H/Q	0.2284	likely_benign	0.2802	benign	-1.377	Destabilizing	0.996	D	0.631	neutral	N	0.488959263	None	None	N
H/R	0.1994	likely_benign	0.2347	benign	-1.255	Destabilizing	0.996	D	0.623	neutral	N	0.460676584	None	None	N
H/S	0.3405	ambiguous	0.4097	ambiguous	-1.78	Destabilizing	0.99	D	0.591	neutral	None	None	None	None	N
H/T	0.311	likely_benign	0.3975	ambiguous	-1.479	Destabilizing	0.99	D	0.657	neutral	None	None	None	None	N
H/V	0.2112	likely_benign	0.2678	benign	-0.676	Destabilizing	0.939	D	0.679	prob.neutral	None	None	None	None	N
H/W	0.463	ambiguous	0.4742	ambiguous	0.848	Stabilizing	0.999	D	0.643	neutral	None	None	None	None	N
H/Y	0.0802	likely_benign	0.0855	benign	0.66	Stabilizing	0.704	D	0.563	neutral	D	0.528979089	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.