TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17206	51841;51842;51843	chr2:178609807;178609806;178609805	chr2:179474534;179474533;179474532
N2AB	15565	46918;46919;46920	chr2:178609807;178609806;178609805	chr2:179474534;179474533;179474532
N2A	14638	44137;44138;44139	chr2:178609807;178609806;178609805	chr2:179474534;179474533;179474532
N2B	8141	24646;24647;24648	chr2:178609807;178609806;178609805	chr2:179474534;179474533;179474532
Novex-1	8266	25021;25022;25023	chr2:178609807;178609806;178609805	chr2:179474534;179474533;179474532
Novex-2	8333	25222;25223;25224	chr2:178609807;178609806;178609805	chr2:179474534;179474533;179474532
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: Fn3-13
• Domain position: 60
• Structural Position: 90
• Q(SASA): 0.3181
• 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/N	rs1305177155	-0.342	0.684	N	0.423	0.271	0.222439326576	gnomAD-2.1.1	2.01E-05	None	None	None	None	N	None	0	1.44827E-04	None	0	0	None	0	None	0	0	0
T/N	rs1305177155	-0.342	0.684	N	0.423	0.271	0.222439326576	gnomAD-3.1.2	6.59E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/N	rs1305177155	-0.342	0.684	N	0.423	0.271	0.222439326576	gnomAD-4.0.0	7.44109E-06	None	None	None	None	N	None	0	1.0014E-04	None	0	0	None	0	0	4.24013E-06	0	1.60241E-05

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	0.163	likely_benign	0.1639	benign	-0.591	Destabilizing	0.309	N	0.371	neutral	N	0.491623061	None	None	N
T/C	0.5152	ambiguous	0.5264	ambiguous	-0.256	Destabilizing	0.02	N	0.328	neutral	None	None	None	None	N
T/D	0.6528	likely_pathogenic	0.6581	pathogenic	-0.369	Destabilizing	0.742	D	0.464	neutral	None	None	None	None	N
T/E	0.5	ambiguous	0.4897	ambiguous	-0.204	Destabilizing	0.742	D	0.464	neutral	None	None	None	None	N
T/F	0.4841	ambiguous	0.4947	ambiguous	-0.546	Destabilizing	0.91	D	0.583	neutral	None	None	None	None	N
T/G	0.4145	ambiguous	0.3958	ambiguous	-0.961	Destabilizing	0.742	D	0.511	neutral	None	None	None	None	N
T/H	0.3352	likely_benign	0.3312	benign	-1.084	Destabilizing	0.996	D	0.572	neutral	None	None	None	None	N
T/I	0.4387	ambiguous	0.4852	ambiguous	0.351	Stabilizing	0.007	N	0.321	neutral	N	0.515019996	None	None	N
T/K	0.3906	ambiguous	0.3876	ambiguous	0.077	Stabilizing	0.742	D	0.461	neutral	None	None	None	None	N
T/L	0.2553	likely_benign	0.2695	benign	0.351	Stabilizing	0.17	N	0.413	neutral	None	None	None	None	N
T/M	0.1781	likely_benign	0.1801	benign	0.15	Stabilizing	0.91	D	0.529	neutral	None	None	None	None	N
T/N	0.1902	likely_benign	0.203	benign	-0.512	Destabilizing	0.684	D	0.423	neutral	N	0.457857204	None	None	N
T/P	0.856	likely_pathogenic	0.8479	pathogenic	0.069	Stabilizing	0.939	D	0.543	neutral	N	0.521849968	None	None	N
T/Q	0.3104	likely_benign	0.2974	benign	-0.309	Destabilizing	0.953	D	0.533	neutral	None	None	None	None	N
T/R	0.3399	likely_benign	0.3374	benign	-0.129	Destabilizing	0.953	D	0.542	neutral	None	None	None	None	N
T/S	0.1256	likely_benign	0.1307	benign	-0.779	Destabilizing	0.034	N	0.187	neutral	N	0.397824679	None	None	N
T/V	0.3066	likely_benign	0.3389	benign	0.069	Stabilizing	0.17	N	0.415	neutral	None	None	None	None	N
T/W	0.7993	likely_pathogenic	0.7935	pathogenic	-0.713	Destabilizing	0.996	D	0.601	neutral	None	None	None	None	N
T/Y	0.445	ambiguous	0.4336	ambiguous	-0.258	Destabilizing	0.953	D	0.586	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.