TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19551	58876;58877;58878	chr2:178593649;178593648;178593647	chr2:179458376;179458375;179458374
N2AB	17910	53953;53954;53955	chr2:178593649;178593648;178593647	chr2:179458376;179458375;179458374
N2A	16983	51172;51173;51174	chr2:178593649;178593648;178593647	chr2:179458376;179458375;179458374
N2B	10486	31681;31682;31683	chr2:178593649;178593648;178593647	chr2:179458376;179458375;179458374
Novex-1	10611	32056;32057;32058	chr2:178593649;178593648;178593647	chr2:179458376;179458375;179458374
Novex-2	10678	32257;32258;32259	chr2:178593649;178593648;178593647	chr2:179458376;179458375;179458374
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-29
• Domain position: 73
• Structural Position: 105
• Q(SASA): 0.1506
• 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
I/V	rs1264084790	None	0.001	N	0.237	0.06	0.302793454619	gnomAD-4.0.0	3.18563E-06	None	None	None	None	N	None	0	0	None	0	5.57569E-05	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
I/A	0.3684	ambiguous	0.3072	benign	-2.144	Highly Destabilizing	0.218	N	0.647	neutral	None	None	None	None	N
I/C	0.581	likely_pathogenic	0.5199	ambiguous	-1.202	Destabilizing	0.973	D	0.675	prob.neutral	None	None	None	None	N
I/D	0.7395	likely_pathogenic	0.6526	pathogenic	-2.229	Highly Destabilizing	0.826	D	0.703	prob.neutral	None	None	None	None	N
I/E	0.503	ambiguous	0.4579	ambiguous	-1.984	Destabilizing	0.404	N	0.679	prob.neutral	None	None	None	None	N
I/F	0.2301	likely_benign	0.1893	benign	-1.171	Destabilizing	0.782	D	0.643	neutral	N	0.44696542	None	None	N
I/G	0.7156	likely_pathogenic	0.6261	pathogenic	-2.697	Highly Destabilizing	0.826	D	0.68	prob.neutral	None	None	None	None	N
I/H	0.4961	ambiguous	0.4289	ambiguous	-2.234	Highly Destabilizing	0.973	D	0.749	deleterious	None	None	None	None	N
I/K	0.3966	ambiguous	0.3406	ambiguous	-1.406	Destabilizing	0.704	D	0.676	prob.neutral	None	None	None	None	N
I/L	0.1136	likely_benign	0.1001	benign	-0.544	Destabilizing	0.084	N	0.487	neutral	N	0.450120369	None	None	N
I/M	0.116	likely_benign	0.1039	benign	-0.498	Destabilizing	0.782	D	0.652	neutral	N	0.475152099	None	None	N
I/N	0.323	likely_benign	0.2589	benign	-1.766	Destabilizing	0.782	D	0.727	prob.delet.	N	0.467953981	None	None	N
I/P	0.9686	likely_pathogenic	0.9607	pathogenic	-1.058	Destabilizing	0.906	D	0.725	prob.delet.	None	None	None	None	N
I/Q	0.3651	ambiguous	0.3293	benign	-1.569	Destabilizing	0.04	N	0.623	neutral	None	None	None	None	N
I/R	0.3277	likely_benign	0.2728	benign	-1.303	Destabilizing	0.704	D	0.716	prob.delet.	None	None	None	None	N
I/S	0.2771	likely_benign	0.2351	benign	-2.465	Highly Destabilizing	0.782	D	0.658	neutral	N	0.448925503	None	None	N
I/T	0.1959	likely_benign	0.1748	benign	-2.074	Highly Destabilizing	0.505	D	0.629	neutral	N	0.454349965	None	None	N
I/V	0.0782	likely_benign	0.0695	benign	-1.058	Destabilizing	0.001	N	0.237	neutral	N	0.411735339	None	None	N
I/W	0.8427	likely_pathogenic	0.7963	pathogenic	-1.59	Destabilizing	0.991	D	0.752	deleterious	None	None	None	None	N
I/Y	0.5188	ambiguous	0.4601	ambiguous	-1.244	Destabilizing	0.906	D	0.671	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.