TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9957	30094;30095;30096	chr2:178704603;178704602;178704601	chr2:179569330;179569329;179569328
N2AB	9640	29143;29144;29145	chr2:178704603;178704602;178704601	chr2:179569330;179569329;179569328
N2A	8713	26362;26363;26364	chr2:178704603;178704602;178704601	chr2:179569330;179569329;179569328
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: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-84
• Domain position: 58
• Structural Position: 137
• Q(SASA): 0.1513
• 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	rs2154291224	None	None	None	0.411	0.098	0.266843984389	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	None	0	0	0	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	0.1581	likely_benign	0.1499	benign	-1.14	Destabilizing	0.037	N	0.427	neutral	None	None	None	None	N
T/C	0.508	ambiguous	0.5435	ambiguous	-0.9	Destabilizing	0.859	D	0.611	neutral	None	None	None	None	N
T/D	0.8234	likely_pathogenic	0.7671	pathogenic	-1.818	Destabilizing	0.364	N	0.635	neutral	None	None	None	None	N
T/E	0.5064	ambiguous	0.4727	ambiguous	-1.567	Destabilizing	0.364	N	0.617	neutral	None	None	None	None	N
T/F	0.3207	likely_benign	0.2883	benign	-0.662	Destabilizing	0.22	N	0.612	neutral	None	None	None	None	N
T/G	0.6286	likely_pathogenic	0.6039	pathogenic	-1.587	Destabilizing	0.364	N	0.615	neutral	None	None	None	None	N
T/H	0.3179	likely_benign	0.3187	benign	-1.658	Destabilizing	0.958	D	0.594	neutral	None	None	None	None	N
T/I	0.0904	likely_benign	0.0929	benign	0.054	Stabilizing	None	N	0.411	neutral	None	None	None	None	N
T/K	0.1952	likely_benign	0.2022	benign	-0.541	Destabilizing	0.301	N	0.622	neutral	None	None	None	None	N
T/L	0.125	likely_benign	0.1158	benign	0.054	Stabilizing	None	N	0.41	neutral	None	None	None	None	N
T/M	0.1167	likely_benign	0.1192	benign	-0.168	Destabilizing	0.497	N	0.615	neutral	None	None	None	None	N
T/N	0.3285	likely_benign	0.2976	benign	-1.411	Destabilizing	0.859	D	0.603	neutral	None	None	None	None	N
T/P	0.9305	likely_pathogenic	0.8793	pathogenic	-0.314	Destabilizing	0.822	D	0.637	neutral	None	None	None	None	N
T/Q	0.3077	likely_benign	0.3025	benign	-1.041	Destabilizing	0.859	D	0.609	neutral	None	None	None	None	N
T/R	0.167	likely_benign	0.1667	benign	-0.9	Destabilizing	0.602	D	0.639	neutral	None	None	None	None	N
T/S	0.2325	likely_benign	0.2215	benign	-1.58	Destabilizing	0.151	N	0.521	neutral	None	None	None	None	N
T/V	0.1114	likely_benign	0.1152	benign	-0.314	Destabilizing	0.004	N	0.468	neutral	None	None	None	None	N
T/W	0.7417	likely_pathogenic	0.7048	pathogenic	-0.936	Destabilizing	0.958	D	0.614	neutral	None	None	None	None	N
T/Y	0.4061	ambiguous	0.3758	ambiguous	-0.504	Destabilizing	0.667	D	0.619	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.