TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20509	61750;61751;61752	chr2:178590200;178590199;178590198	chr2:179454927;179454926;179454925
N2AB	18868	56827;56828;56829	chr2:178590200;178590199;178590198	chr2:179454927;179454926;179454925
N2A	17941	54046;54047;54048	chr2:178590200;178590199;178590198	chr2:179454927;179454926;179454925
N2B	11444	34555;34556;34557	chr2:178590200;178590199;178590198	chr2:179454927;179454926;179454925
Novex-1	11569	34930;34931;34932	chr2:178590200;178590199;178590198	chr2:179454927;179454926;179454925
Novex-2	11636	35131;35132;35133	chr2:178590200;178590199;178590198	chr2:179454927;179454926;179454925
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-121
• Domain position: 31
• Structural Position: 47
• Q(SASA): 0.3816
• 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/S	None	None	0.669	N	0.57	0.093	0.180583059064	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
T/A	0.0938	likely_benign	0.1	benign	-0.879	Destabilizing	0.012	N	0.299	neutral	N	0.487124815	None	None	N
T/C	0.3155	likely_benign	0.3164	benign	-0.477	Destabilizing	0.993	D	0.571	neutral	None	None	None	None	N
T/D	0.4677	ambiguous	0.5471	ambiguous	0.094	Stabilizing	0.974	D	0.58	neutral	None	None	None	None	N
T/E	0.3333	likely_benign	0.3802	ambiguous	0.111	Stabilizing	0.949	D	0.569	neutral	None	None	None	None	N
T/F	0.2021	likely_benign	0.2025	benign	-0.929	Destabilizing	0.949	D	0.619	neutral	None	None	None	None	N
T/G	0.3012	likely_benign	0.3317	benign	-1.15	Destabilizing	0.728	D	0.588	neutral	None	None	None	None	N
T/H	0.2356	likely_benign	0.2483	benign	-1.354	Destabilizing	0.998	D	0.615	neutral	None	None	None	None	N
T/I	0.1156	likely_benign	0.1131	benign	-0.245	Destabilizing	0.051	N	0.317	neutral	N	0.511126834	None	None	N
T/K	0.2634	likely_benign	0.3107	benign	-0.554	Destabilizing	0.949	D	0.569	neutral	None	None	None	None	N
T/L	0.0889	likely_benign	0.0874	benign	-0.245	Destabilizing	0.016	N	0.313	neutral	None	None	None	None	N
T/M	0.0944	likely_benign	0.0925	benign	-0.044	Destabilizing	0.949	D	0.601	neutral	None	None	None	None	N
T/N	0.1313	likely_benign	0.1468	benign	-0.529	Destabilizing	0.966	D	0.577	neutral	N	0.495709643	None	None	N
T/P	0.6804	likely_pathogenic	0.7545	pathogenic	-0.424	Destabilizing	0.966	D	0.591	neutral	D	0.537286978	None	None	N
T/Q	0.2301	likely_benign	0.2463	benign	-0.638	Destabilizing	0.974	D	0.593	neutral	None	None	None	None	N
T/R	0.2142	likely_benign	0.254	benign	-0.386	Destabilizing	0.974	D	0.591	neutral	None	None	None	None	N
T/S	0.1013	likely_benign	0.1054	benign	-0.873	Destabilizing	0.669	D	0.57	neutral	N	0.503040494	None	None	N
T/V	0.1089	likely_benign	0.1075	benign	-0.424	Destabilizing	0.525	D	0.554	neutral	None	None	None	None	N
T/W	0.6313	likely_pathogenic	0.6344	pathogenic	-0.849	Destabilizing	0.998	D	0.662	neutral	None	None	None	None	N
T/Y	0.2763	likely_benign	0.278	benign	-0.607	Destabilizing	0.991	D	0.626	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.