TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33178	99757;99758;99759	chr2:178537675;178537674;178537673	chr2:179402402;179402401;179402400
N2AB	31537	94834;94835;94836	chr2:178537675;178537674;178537673	chr2:179402402;179402401;179402400
N2A	30610	92053;92054;92055	chr2:178537675;178537674;178537673	chr2:179402402;179402401;179402400
N2B	24113	72562;72563;72564	chr2:178537675;178537674;178537673	chr2:179402402;179402401;179402400
Novex-1	24238	72937;72938;72939	chr2:178537675;178537674;178537673	chr2:179402402;179402401;179402400
Novex-2	24305	73138;73139;73140	chr2:178537675;178537674;178537673	chr2:179402402;179402401;179402400
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-156
• Domain position: 78
• Structural Position: 162
• Q(SASA): 0.7004
• 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/K	rs371017136	0.8	0.812	N	0.507	0.341	None	gnomAD-2.1.1	7.13E-06	None	None	None	None	I	None	8.27E-05	0	None	0	0	None	0	None	0	0	0
E/K	rs371017136	0.8	0.812	N	0.507	0.341	None	gnomAD-3.1.2	1.97E-05	None	None	None	None	I	None	7.24E-05	0	0	0	0	None	0	0	0	0	0
E/K	rs371017136	0.8	0.812	N	0.507	0.341	None	gnomAD-4.0.0	1.97122E-05	None	None	None	None	I	None	7.23554E-05	0	None	0	0	None	0	0	0	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	0.1948	likely_benign	0.2616	benign	-0.045	Destabilizing	0.7	D	0.514	neutral	N	0.475667466	None	None	I
E/C	0.9016	likely_pathogenic	0.9484	pathogenic	-0.124	Destabilizing	0.996	D	0.728	prob.delet.	None	None	None	None	I
E/D	0.066	likely_benign	0.0815	benign	-0.317	Destabilizing	None	N	0.3	neutral	N	0.469992287	None	None	I
E/F	0.8618	likely_pathogenic	0.9326	pathogenic	-0.064	Destabilizing	0.998	D	0.634	neutral	None	None	None	None	I
E/G	0.2147	likely_benign	0.2997	benign	-0.174	Destabilizing	0.886	D	0.424	neutral	N	0.498544326	None	None	I
E/H	0.6198	likely_pathogenic	0.7435	pathogenic	0.485	Stabilizing	0.997	D	0.563	neutral	None	None	None	None	I
E/I	0.5062	ambiguous	0.6465	pathogenic	0.24	Stabilizing	0.95	D	0.642	neutral	None	None	None	None	I
E/K	0.3151	likely_benign	0.4071	ambiguous	0.463	Stabilizing	0.812	D	0.507	neutral	N	0.496349383	None	None	I
E/L	0.5598	ambiguous	0.6966	pathogenic	0.24	Stabilizing	0.95	D	0.616	neutral	None	None	None	None	I
E/M	0.6239	likely_pathogenic	0.7591	pathogenic	0.056	Stabilizing	0.975	D	0.599	neutral	None	None	None	None	I
E/N	0.2332	likely_benign	0.3306	benign	0.183	Stabilizing	0.686	D	0.524	neutral	None	None	None	None	I
E/P	0.5759	likely_pathogenic	0.6618	pathogenic	0.163	Stabilizing	0.739	D	0.527	neutral	None	None	None	None	I
E/Q	0.2647	likely_benign	0.3437	ambiguous	0.2	Stabilizing	0.957	D	0.505	neutral	D	0.52584557	None	None	I
E/R	0.4858	ambiguous	0.5947	pathogenic	0.684	Stabilizing	0.976	D	0.563	neutral	None	None	None	None	I
E/S	0.2128	likely_benign	0.2935	benign	0.057	Stabilizing	0.756	D	0.495	neutral	None	None	None	None	I
E/T	0.291	likely_benign	0.3915	ambiguous	0.17	Stabilizing	0.937	D	0.492	neutral	None	None	None	None	I
E/V	0.3273	likely_benign	0.4416	ambiguous	0.163	Stabilizing	0.911	D	0.551	neutral	N	0.519535673	None	None	I
E/W	0.9546	likely_pathogenic	0.979	pathogenic	-0.006	Destabilizing	0.999	D	0.733	prob.delet.	None	None	None	None	I
E/Y	0.7502	likely_pathogenic	0.8597	pathogenic	0.164	Stabilizing	0.999	D	0.581	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.