TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24255	72988;72989;72990	chr2:178573369;178573368;178573367	chr2:179438096;179438095;179438094
N2AB	22614	68065;68066;68067	chr2:178573369;178573368;178573367	chr2:179438096;179438095;179438094
N2A	21687	65284;65285;65286	chr2:178573369;178573368;178573367	chr2:179438096;179438095;179438094
N2B	15190	45793;45794;45795	chr2:178573369;178573368;178573367	chr2:179438096;179438095;179438094
Novex-1	15315	46168;46169;46170	chr2:178573369;178573368;178573367	chr2:179438096;179438095;179438094
Novex-2	15382	46369;46370;46371	chr2:178573369;178573368;178573367	chr2:179438096;179438095;179438094
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-64
• Domain position: 34
• Structural Position: 36
• Q(SASA): 0.3147
• 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
I/V	None	None	0.005	N	0.158	0.128	0.400033932507	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	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
I/A	0.137	likely_benign	0.1377	benign	-1.226	Destabilizing	0.007	N	0.215	neutral	None	None	None	None	I
I/C	0.364	ambiguous	0.3658	ambiguous	-0.702	Destabilizing	0.356	N	0.323	neutral	None	None	None	None	I
I/D	0.3415	ambiguous	0.373	ambiguous	-0.869	Destabilizing	0.016	N	0.267	neutral	None	None	None	None	I
I/E	0.2359	likely_benign	0.2639	benign	-0.949	Destabilizing	0.031	N	0.265	neutral	None	None	None	None	I
I/F	0.108	likely_benign	0.1133	benign	-1.166	Destabilizing	0.106	N	0.327	neutral	N	0.47967367	None	None	I
I/G	0.2654	likely_benign	0.27	benign	-1.45	Destabilizing	0.031	N	0.285	neutral	None	None	None	None	I
I/H	0.2038	likely_benign	0.2137	benign	-0.693	Destabilizing	0.356	N	0.321	neutral	None	None	None	None	I
I/K	0.1288	likely_benign	0.1362	benign	-0.656	Destabilizing	0.031	N	0.297	neutral	None	None	None	None	I
I/L	0.0711	likely_benign	0.0736	benign	-0.729	Destabilizing	0.005	N	0.147	neutral	N	0.41398621	None	None	I
I/M	0.0723	likely_benign	0.0739	benign	-0.434	Destabilizing	0.295	N	0.325	neutral	N	0.518692232	None	None	I
I/N	0.0917	likely_benign	0.097	benign	-0.383	Destabilizing	None	N	0.231	neutral	N	0.488369325	None	None	I
I/P	0.7036	likely_pathogenic	0.7238	pathogenic	-0.862	Destabilizing	0.136	N	0.393	neutral	None	None	None	None	I
I/Q	0.151	likely_benign	0.1654	benign	-0.701	Destabilizing	0.136	N	0.386	neutral	None	None	None	None	I
I/R	0.1103	likely_benign	0.1201	benign	0.011	Stabilizing	0.072	N	0.357	neutral	None	None	None	None	I
I/S	0.0987	likely_benign	0.1015	benign	-0.89	Destabilizing	0.005	N	0.231	neutral	N	0.41604508	None	None	I
I/T	0.0706	likely_benign	0.072	benign	-0.866	Destabilizing	None	N	0.153	neutral	N	0.376254541	None	None	I
I/V	0.0678	likely_benign	0.0671	benign	-0.862	Destabilizing	0.005	N	0.158	neutral	N	0.473053156	None	None	I
I/W	0.5824	likely_pathogenic	0.5878	pathogenic	-1.15	Destabilizing	0.864	D	0.32	neutral	None	None	None	None	I
I/Y	0.3246	likely_benign	0.3386	benign	-0.907	Destabilizing	0.356	N	0.406	neutral	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.