TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1166	3721;3722;3723	chr2:178781148;178781147;178781146	chr2:179645875;179645874;179645873
N2AB	1166	3721;3722;3723	chr2:178781148;178781147;178781146	chr2:179645875;179645874;179645873
N2A	1166	3721;3722;3723	chr2:178781148;178781147;178781146	chr2:179645875;179645874;179645873
N2B	1120	3583;3584;3585	chr2:178781148;178781147;178781146	chr2:179645875;179645874;179645873
Novex-1	1120	3583;3584;3585	chr2:178781148;178781147;178781146	chr2:179645875;179645874;179645873
Novex-2	1120	3583;3584;3585	chr2:178781148;178781147;178781146	chr2:179645875;179645874;179645873
Novex-3	1166	3721;3722;3723	chr2:178781148;178781147;178781146	chr2:179645875;179645874;179645873

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-4
• Domain position: 85
• Structural Position: 168
• Q(SASA): 0.3913
• 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
S/F	rs374543837	-0.79	0.89	N	0.692	0.411	None	gnomAD-2.1.1	3.98E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.82E-06	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
S/A	0.0964	likely_benign	0.0983	benign	-0.544	Destabilizing	0.006	N	0.275	neutral	N	0.51269278	None	None	I
S/C	0.2326	likely_benign	0.2349	benign	-0.401	Destabilizing	0.997	D	0.658	neutral	N	0.50731666	None	None	I
S/D	0.8092	likely_pathogenic	0.8521	pathogenic	0.465	Stabilizing	0.978	D	0.488	neutral	None	None	None	None	I
S/E	0.6972	likely_pathogenic	0.7492	pathogenic	0.426	Stabilizing	0.86	D	0.475	neutral	None	None	None	None	I
S/F	0.3009	likely_benign	0.3546	ambiguous	-0.963	Destabilizing	0.89	D	0.692	prob.neutral	N	0.505956598	None	None	I
S/G	0.2362	likely_benign	0.2617	benign	-0.725	Destabilizing	0.559	D	0.513	neutral	None	None	None	None	I
S/H	0.5531	ambiguous	0.6033	pathogenic	-1.12	Destabilizing	0.956	D	0.677	prob.neutral	None	None	None	None	I
S/I	0.2731	likely_benign	0.3146	benign	-0.187	Destabilizing	0.956	D	0.662	neutral	None	None	None	None	I
S/K	0.8524	likely_pathogenic	0.8877	pathogenic	-0.367	Destabilizing	0.86	D	0.472	neutral	None	None	None	None	I
S/L	0.1774	likely_benign	0.2076	benign	-0.187	Destabilizing	0.754	D	0.587	neutral	None	None	None	None	I
S/M	0.2793	likely_benign	0.3058	benign	-0.13	Destabilizing	0.998	D	0.67	neutral	None	None	None	None	I
S/N	0.3735	ambiguous	0.44	ambiguous	-0.259	Destabilizing	0.978	D	0.533	neutral	None	None	None	None	I
S/P	0.9391	likely_pathogenic	0.971	pathogenic	-0.275	Destabilizing	0.97	D	0.679	prob.neutral	D	0.615156785	None	None	I
S/Q	0.658	likely_pathogenic	0.7023	pathogenic	-0.385	Destabilizing	0.978	D	0.529	neutral	None	None	None	None	I
S/R	0.7789	likely_pathogenic	0.8245	pathogenic	-0.263	Destabilizing	0.978	D	0.677	prob.neutral	None	None	None	None	I
S/T	0.0937	likely_benign	0.1023	benign	-0.349	Destabilizing	0.822	D	0.511	neutral	N	0.445060701	None	None	I
S/V	0.2277	likely_benign	0.2536	benign	-0.275	Destabilizing	0.754	D	0.605	neutral	None	None	None	None	I
S/W	0.5964	likely_pathogenic	0.6481	pathogenic	-0.954	Destabilizing	0.994	D	0.739	prob.delet.	None	None	None	None	I
S/Y	0.3223	likely_benign	0.3712	ambiguous	-0.66	Destabilizing	0.032	N	0.537	neutral	N	0.511706	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.