TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14308	43147;43148;43149	chr2:178633437;178633436;178633435	chr2:179498164;179498163;179498162
N2AB	12667	38224;38225;38226	chr2:178633437;178633436;178633435	chr2:179498164;179498163;179498162
N2A	11740	35443;35444;35445	chr2:178633437;178633436;178633435	chr2:179498164;179498163;179498162
N2B	5243	15952;15953;15954	chr2:178633437;178633436;178633435	chr2:179498164;179498163;179498162
Novex-1	5368	16327;16328;16329	chr2:178633437;178633436;178633435	chr2:179498164;179498163;179498162
Novex-2	5435	16528;16529;16530	chr2:178633437;178633436;178633435	chr2:179498164;179498163;179498162
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-93
• Domain position: 78
• Structural Position: 169
• Q(SASA): 0.1344
• 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
T/I	None	None	1.0	D	0.876	0.446	0.661252799969	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.9375E-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	0.4817	ambiguous	0.3802	ambiguous	-0.986	Destabilizing	0.999	D	0.546	neutral	N	0.501877248	None	None	N
T/C	0.898	likely_pathogenic	0.7994	pathogenic	-0.584	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
T/D	0.9623	likely_pathogenic	0.9438	pathogenic	-1.097	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
T/E	0.9449	likely_pathogenic	0.9203	pathogenic	-0.935	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
T/F	0.9686	likely_pathogenic	0.939	pathogenic	-0.499	Destabilizing	1.0	D	0.916	deleterious	None	None	None	None	N
T/G	0.7438	likely_pathogenic	0.6599	pathogenic	-1.392	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
T/H	0.9586	likely_pathogenic	0.9367	pathogenic	-1.458	Destabilizing	1.0	D	0.904	deleterious	None	None	None	None	N
T/I	0.9124	likely_pathogenic	0.852	pathogenic	0.07	Stabilizing	1.0	D	0.876	deleterious	D	0.62215508	None	None	N
T/K	0.9722	likely_pathogenic	0.9562	pathogenic	-0.72	Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
T/L	0.748	likely_pathogenic	0.6584	pathogenic	0.07	Stabilizing	0.999	D	0.735	prob.delet.	None	None	None	None	N
T/M	0.5085	ambiguous	0.4008	ambiguous	0.089	Stabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
T/N	0.7312	likely_pathogenic	0.6307	pathogenic	-1.193	Destabilizing	1.0	D	0.699	prob.neutral	D	0.753246677	None	None	N
T/P	0.9404	likely_pathogenic	0.9384	pathogenic	-0.25	Destabilizing	1.0	D	0.881	deleterious	D	0.754631704	None	None	N
T/Q	0.9346	likely_pathogenic	0.8909	pathogenic	-1.015	Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
T/R	0.9643	likely_pathogenic	0.9424	pathogenic	-0.801	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
T/S	0.391	ambiguous	0.3111	benign	-1.433	Destabilizing	0.999	D	0.518	neutral	N	0.508387648	None	None	N
T/V	0.7821	likely_pathogenic	0.6925	pathogenic	-0.25	Destabilizing	0.999	D	0.559	neutral	None	None	None	None	N
T/W	0.9919	likely_pathogenic	0.9856	pathogenic	-0.646	Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
T/Y	0.97	likely_pathogenic	0.9449	pathogenic	-0.315	Destabilizing	1.0	D	0.911	deleterious	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.