TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5173	15742;15743;15744	chr2:178733872;178733871;178733870	chr2:179598599;179598598;179598597
N2AB	4856	14791;14792;14793	chr2:178733872;178733871;178733870	chr2:179598599;179598598;179598597
N2A	3929	12010;12011;12012	chr2:178733872;178733871;178733870	chr2:179598599;179598598;179598597
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-35
• Domain position: 6
• Structural Position: 7
• Q(SASA): 0.407
• 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
K/T	None	None	0.99	D	0.599	0.397	0.530109961917	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
K/A	0.4676	ambiguous	0.6152	pathogenic	-0.398	Destabilizing	0.993	D	0.551	neutral	None	None	None	None	N
K/C	0.843	likely_pathogenic	0.923	pathogenic	-0.415	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
K/D	0.6964	likely_pathogenic	0.7841	pathogenic	0.528	Stabilizing	0.998	D	0.609	neutral	None	None	None	None	N
K/E	0.3286	likely_benign	0.4338	ambiguous	0.602	Stabilizing	0.98	D	0.537	neutral	N	0.507166245	None	None	N
K/F	0.8695	likely_pathogenic	0.9338	pathogenic	-0.291	Destabilizing	0.999	D	0.718	prob.delet.	None	None	None	None	N
K/G	0.5449	ambiguous	0.6889	pathogenic	-0.693	Destabilizing	0.993	D	0.579	neutral	None	None	None	None	N
K/H	0.4031	ambiguous	0.529	ambiguous	-0.938	Destabilizing	0.999	D	0.675	neutral	None	None	None	None	N
K/I	0.5693	likely_pathogenic	0.7274	pathogenic	0.334	Stabilizing	0.999	D	0.727	prob.delet.	D	0.596702649	None	None	N
K/L	0.5259	ambiguous	0.6781	pathogenic	0.334	Stabilizing	0.993	D	0.579	neutral	None	None	None	None	N
K/M	0.3483	ambiguous	0.4632	ambiguous	0.143	Stabilizing	1.0	D	0.669	neutral	None	None	None	None	N
K/N	0.5144	ambiguous	0.6472	pathogenic	0.075	Stabilizing	0.997	D	0.557	neutral	D	0.587072243	None	None	N
K/P	0.5247	ambiguous	0.6358	pathogenic	0.12	Stabilizing	0.999	D	0.672	neutral	None	None	None	None	N
K/Q	0.1914	likely_benign	0.277	benign	-0.034	Destabilizing	0.994	D	0.569	neutral	D	0.544413368	None	None	N
K/R	0.0841	likely_benign	0.1039	benign	-0.165	Destabilizing	0.061	N	0.169	neutral	N	0.514815774	None	None	N
K/S	0.5733	likely_pathogenic	0.7207	pathogenic	-0.652	Destabilizing	0.993	D	0.528	neutral	None	None	None	None	N
K/T	0.2979	likely_benign	0.4255	ambiguous	-0.383	Destabilizing	0.99	D	0.599	neutral	D	0.556409469	None	None	N
K/V	0.525	ambiguous	0.6756	pathogenic	0.12	Stabilizing	0.998	D	0.603	neutral	None	None	None	None	N
K/W	0.827	likely_pathogenic	0.9121	pathogenic	-0.157	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
K/Y	0.7219	likely_pathogenic	0.8306	pathogenic	0.147	Stabilizing	0.999	D	0.721	prob.delet.	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.