TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24731	74416;74417;74418	chr2:178571941;178571940;178571939	chr2:179436668;179436667;179436666
N2AB	23090	69493;69494;69495	chr2:178571941;178571940;178571939	chr2:179436668;179436667;179436666
N2A	22163	66712;66713;66714	chr2:178571941;178571940;178571939	chr2:179436668;179436667;179436666
N2B	15666	47221;47222;47223	chr2:178571941;178571940;178571939	chr2:179436668;179436667;179436666
Novex-1	15791	47596;47597;47598	chr2:178571941;178571940;178571939	chr2:179436668;179436667;179436666
Novex-2	15858	47797;47798;47799	chr2:178571941;178571940;178571939	chr2:179436668;179436667;179436666
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-133
• Domain position: 16
• Structural Position: 25
• Q(SASA): 0.7317
• 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
E/G	rs76565211	-0.218	0.822	N	0.49	0.282	None	gnomAD-4.0.0	3.18789E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.79435E-05	0	0	0	0
E/K	rs186780326	0.903	0.822	N	0.436	0.311	None	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	0	None	0	5.63E-05	None	0	None	0	0	0
E/K	rs186780326	0.903	0.822	N	0.436	0.311	None	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	1.93349E-04	None	0	0	0	0	0
E/K	rs186780326	0.903	0.822	N	0.436	0.311	None	1000 genomes	1.99681E-04	None	None	None	None	I	None	0	0	None	None	1E-03	0	None	None	None	0	None
E/K	rs186780326	0.903	0.822	N	0.436	0.311	None	gnomAD-4.0.0	4.33916E-06	None	None	None	None	I	None	0	0	None	0	8.94694E-05	None	0	0	0	0	4.80446E-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
E/A	0.2728	likely_benign	0.2818	benign	-0.435	Destabilizing	0.822	D	0.476	neutral	N	0.470775084	None	None	I
E/C	0.8867	likely_pathogenic	0.8898	pathogenic	0.058	Stabilizing	0.998	D	0.695	prob.neutral	None	None	None	None	I
E/D	0.1146	likely_benign	0.1138	benign	-0.367	Destabilizing	0.002	N	0.172	neutral	N	0.447647706	None	None	I
E/F	0.8876	likely_pathogenic	0.8972	pathogenic	-0.363	Destabilizing	0.993	D	0.593	neutral	None	None	None	None	I
E/G	0.2373	likely_benign	0.2452	benign	-0.649	Destabilizing	0.822	D	0.49	neutral	N	0.454770742	None	None	I
E/H	0.547	ambiguous	0.5815	pathogenic	-0.296	Destabilizing	0.993	D	0.357	neutral	None	None	None	None	I
E/I	0.6652	likely_pathogenic	0.6933	pathogenic	0.097	Stabilizing	0.978	D	0.581	neutral	None	None	None	None	I
E/K	0.1788	likely_benign	0.1966	benign	0.261	Stabilizing	0.822	D	0.436	neutral	N	0.498500601	None	None	I
E/L	0.6763	likely_pathogenic	0.6946	pathogenic	0.097	Stabilizing	0.978	D	0.565	neutral	None	None	None	None	I
E/M	0.6187	likely_pathogenic	0.641	pathogenic	0.332	Stabilizing	0.998	D	0.551	neutral	None	None	None	None	I
E/N	0.2537	likely_benign	0.259	benign	0.006	Stabilizing	0.754	D	0.41	neutral	None	None	None	None	I
E/P	0.9615	likely_pathogenic	0.9695	pathogenic	-0.06	Destabilizing	0.978	D	0.407	neutral	None	None	None	None	I
E/Q	0.1661	likely_benign	0.1741	benign	0.04	Stabilizing	0.904	D	0.398	neutral	N	0.4804722	None	None	I
E/R	0.3383	likely_benign	0.3724	ambiguous	0.406	Stabilizing	0.978	D	0.373	neutral	None	None	None	None	I
E/S	0.2317	likely_benign	0.2446	benign	-0.185	Destabilizing	0.86	D	0.417	neutral	None	None	None	None	I
E/T	0.316	likely_benign	0.3407	ambiguous	-0.012	Destabilizing	0.86	D	0.426	neutral	None	None	None	None	I
E/V	0.4292	ambiguous	0.4559	ambiguous	-0.06	Destabilizing	0.97	D	0.473	neutral	N	0.483398837	None	None	I
E/W	0.958	likely_pathogenic	0.9635	pathogenic	-0.223	Destabilizing	0.998	D	0.713	prob.delet.	None	None	None	None	I
E/Y	0.7501	likely_pathogenic	0.7668	pathogenic	-0.122	Destabilizing	0.993	D	0.536	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.