TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19611	59056;59057;59058	chr2:178593377;178593376;178593375	chr2:179458104;179458103;179458102
N2AB	17970	54133;54134;54135	chr2:178593377;178593376;178593375	chr2:179458104;179458103;179458102
N2A	17043	51352;51353;51354	chr2:178593377;178593376;178593375	chr2:179458104;179458103;179458102
N2B	10546	31861;31862;31863	chr2:178593377;178593376;178593375	chr2:179458104;179458103;179458102
Novex-1	10671	32236;32237;32238	chr2:178593377;178593376;178593375	chr2:179458104;179458103;179458102
Novex-2	10738	32437;32438;32439	chr2:178593377;178593376;178593375	chr2:179458104;179458103;179458102
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-30
• Domain position: 33
• Structural Position: 36
• Q(SASA): 0.3892
• 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
T/K	None	None	0.018	N	0.275	0.296	0.273503213844	gnomAD-4.0.0	1.20034E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.31253E-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
T/A	0.1298	likely_benign	0.1178	benign	-0.664	Destabilizing	0.565	D	0.522	neutral	N	0.502478867	None	None	I
T/C	0.4365	ambiguous	0.4284	ambiguous	-0.352	Destabilizing	0.996	D	0.659	neutral	None	None	None	None	I
T/D	0.5318	ambiguous	0.5146	ambiguous	-0.698	Destabilizing	0.923	D	0.599	neutral	None	None	None	None	I
T/E	0.3447	ambiguous	0.3331	benign	-0.689	Destabilizing	0.633	D	0.569	neutral	None	None	None	None	I
T/F	0.2829	likely_benign	0.2787	benign	-0.603	Destabilizing	0.024	N	0.364	neutral	None	None	None	None	I
T/G	0.3073	likely_benign	0.2983	benign	-0.947	Destabilizing	0.775	D	0.591	neutral	None	None	None	None	I
T/H	0.281	likely_benign	0.2767	benign	-1.279	Destabilizing	0.989	D	0.713	prob.delet.	None	None	None	None	I
T/I	0.1686	likely_benign	0.159	benign	0.007	Stabilizing	0.82	D	0.591	neutral	N	0.49731967	None	None	I
T/K	0.1753	likely_benign	0.1695	benign	-0.943	Destabilizing	0.018	N	0.275	neutral	N	0.472511328	None	None	I
T/L	0.1021	likely_benign	0.1044	benign	0.007	Stabilizing	0.633	D	0.529	neutral	None	None	None	None	I
T/M	0.1071	likely_benign	0.1012	benign	0.324	Stabilizing	0.989	D	0.653	neutral	None	None	None	None	I
T/N	0.1583	likely_benign	0.153	benign	-0.874	Destabilizing	0.923	D	0.549	neutral	None	None	None	None	I
T/P	0.6655	likely_pathogenic	0.6299	pathogenic	-0.184	Destabilizing	0.949	D	0.669	neutral	D	0.528940915	None	None	I
T/Q	0.2128	likely_benign	0.2068	benign	-1.006	Destabilizing	0.858	D	0.665	neutral	None	None	None	None	I
T/R	0.152	likely_benign	0.1426	benign	-0.703	Destabilizing	0.82	D	0.592	neutral	N	0.482817676	None	None	I
T/S	0.1402	likely_benign	0.1363	benign	-1.036	Destabilizing	0.565	D	0.517	neutral	N	0.47282727	None	None	I
T/V	0.1511	likely_benign	0.1459	benign	-0.184	Destabilizing	0.775	D	0.483	neutral	None	None	None	None	I
T/W	0.6123	likely_pathogenic	0.6082	pathogenic	-0.618	Destabilizing	0.996	D	0.764	deleterious	None	None	None	None	I
T/Y	0.34	ambiguous	0.3381	benign	-0.398	Destabilizing	0.858	D	0.727	prob.delet.	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.