TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30256	90991;90992;90993	chr2:178552134;178552133;178552132	chr2:179416861;179416860;179416859
N2AB	28615	86068;86069;86070	chr2:178552134;178552133;178552132	chr2:179416861;179416860;179416859
N2A	27688	83287;83288;83289	chr2:178552134;178552133;178552132	chr2:179416861;179416860;179416859
N2B	21191	63796;63797;63798	chr2:178552134;178552133;178552132	chr2:179416861;179416860;179416859
Novex-1	21316	64171;64172;64173	chr2:178552134;178552133;178552132	chr2:179416861;179416860;179416859
Novex-2	21383	64372;64373;64374	chr2:178552134;178552133;178552132	chr2:179416861;179416860;179416859
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: Fn3-108
• Domain position: 33
• Structural Position: 34
• Q(SASA): 0.706
• 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/A	None	None	0.999	N	0.623	0.533	0.345405024496	gnomAD-4.0.0	6.84213E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99452E-07	0	0
E/K	None	None	0.999	N	0.599	0.389	0.296329037015	gnomAD-4.0.0	1.20056E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31268E-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	0.2967	likely_benign	0.2743	benign	-0.11	Destabilizing	0.999	D	0.623	neutral	N	0.471594506	None	None	N
E/C	0.9073	likely_pathogenic	0.9015	pathogenic	-0.08	Destabilizing	1.0	D	0.667	neutral	None	None	None	None	N
E/D	0.0815	likely_benign	0.081	benign	-0.196	Destabilizing	0.999	D	0.429	neutral	N	0.471074431	None	None	N
E/F	0.8733	likely_pathogenic	0.8659	pathogenic	-0.052	Destabilizing	1.0	D	0.593	neutral	None	None	None	None	N
E/G	0.3634	ambiguous	0.3417	ambiguous	-0.262	Destabilizing	1.0	D	0.626	neutral	N	0.469726624	None	None	N
E/H	0.6715	likely_pathogenic	0.6507	pathogenic	0.434	Stabilizing	1.0	D	0.669	neutral	None	None	None	None	N
E/I	0.4872	ambiguous	0.4972	ambiguous	0.24	Stabilizing	1.0	D	0.623	neutral	None	None	None	None	N
E/K	0.3356	likely_benign	0.334	benign	0.472	Stabilizing	0.999	D	0.599	neutral	N	0.487505321	None	None	N
E/L	0.5828	likely_pathogenic	0.589	pathogenic	0.24	Stabilizing	1.0	D	0.633	neutral	None	None	None	None	N
E/M	0.6333	likely_pathogenic	0.6331	pathogenic	0.116	Stabilizing	1.0	D	0.603	neutral	None	None	None	None	N
E/N	0.2863	likely_benign	0.2724	benign	0.179	Stabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
E/P	0.5574	ambiguous	0.5382	ambiguous	0.143	Stabilizing	1.0	D	0.65	neutral	None	None	None	None	N
E/Q	0.2683	likely_benign	0.2598	benign	0.211	Stabilizing	1.0	D	0.616	neutral	N	0.441869032	None	None	N
E/R	0.5112	ambiguous	0.499	ambiguous	0.703	Stabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
E/S	0.3243	likely_benign	0.3006	benign	0.026	Stabilizing	0.999	D	0.654	neutral	None	None	None	None	N
E/T	0.3794	ambiguous	0.36	ambiguous	0.158	Stabilizing	1.0	D	0.671	neutral	None	None	None	None	N
E/V	0.3311	likely_benign	0.3355	benign	0.143	Stabilizing	1.0	D	0.664	neutral	N	0.480322461	None	None	N
E/W	0.956	likely_pathogenic	0.953	pathogenic	0.043	Stabilizing	1.0	D	0.671	neutral	None	None	None	None	N
E/Y	0.763	likely_pathogenic	0.7508	pathogenic	0.186	Stabilizing	1.0	D	0.625	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.