TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29456	88591;88592;88593	chr2:178555093;178555092;178555091	chr2:179419820;179419819;179419818
N2AB	27815	83668;83669;83670	chr2:178555093;178555092;178555091	chr2:179419820;179419819;179419818
N2A	26888	80887;80888;80889	chr2:178555093;178555092;178555091	chr2:179419820;179419819;179419818
N2B	20391	61396;61397;61398	chr2:178555093;178555092;178555091	chr2:179419820;179419819;179419818
Novex-1	20516	61771;61772;61773	chr2:178555093;178555092;178555091	chr2:179419820;179419819;179419818
Novex-2	20583	61972;61973;61974	chr2:178555093;178555092;178555091	chr2:179419820;179419819;179419818
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-146
• Domain position: 13
• Structural Position: 25
• Q(SASA): 0.4049
• 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	rs1468721085	-0.529	0.934	N	0.358	0.273	0.265929055128	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
T/I	rs1468721085	-0.529	0.934	N	0.358	0.273	0.265929055128	gnomAD-4.0.0	1.85916E-06	None	None	None	None	N	None	1.33515E-05	0	None	0	0	None	0	0	1.69523E-06	0	0
T/R	rs1468721085	None	0.966	N	0.378	0.375	0.284539287134	gnomAD-4.0.0	1.36844E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79895E-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	0.086	likely_benign	0.0844	benign	-0.95	Destabilizing	0.005	N	0.205	neutral	N	0.431176743	None	None	N
T/C	0.403	ambiguous	0.416	ambiguous	-0.485	Destabilizing	0.998	D	0.363	neutral	None	None	None	None	N
T/D	0.3311	likely_benign	0.3395	benign	0.181	Stabilizing	0.842	D	0.382	neutral	None	None	None	None	N
T/E	0.2737	likely_benign	0.2811	benign	0.152	Stabilizing	0.842	D	0.326	neutral	None	None	None	None	N
T/F	0.3014	likely_benign	0.2886	benign	-1.295	Destabilizing	0.991	D	0.458	neutral	None	None	None	None	N
T/G	0.2346	likely_benign	0.2426	benign	-1.146	Destabilizing	0.525	D	0.371	neutral	None	None	None	None	N
T/H	0.2877	likely_benign	0.2808	benign	-1.468	Destabilizing	0.998	D	0.443	neutral	None	None	None	None	N
T/I	0.2433	likely_benign	0.2377	benign	-0.53	Destabilizing	0.934	D	0.358	neutral	N	0.484472511	None	None	N
T/K	0.2338	likely_benign	0.2336	benign	-0.508	Destabilizing	0.801	D	0.339	neutral	N	0.434350335	None	None	N
T/L	0.1361	likely_benign	0.135	benign	-0.53	Destabilizing	0.842	D	0.323	neutral	None	None	None	None	N
T/M	0.1095	likely_benign	0.1015	benign	-0.121	Destabilizing	0.991	D	0.365	neutral	None	None	None	None	N
T/N	0.1214	likely_benign	0.1238	benign	-0.364	Destabilizing	0.842	D	0.371	neutral	None	None	None	None	N
T/P	0.6078	likely_pathogenic	0.5986	pathogenic	-0.64	Destabilizing	0.966	D	0.371	neutral	N	0.484125794	None	None	N
T/Q	0.2219	likely_benign	0.2243	benign	-0.58	Destabilizing	0.974	D	0.385	neutral	None	None	None	None	N
T/R	0.223	likely_benign	0.2205	benign	-0.288	Destabilizing	0.966	D	0.378	neutral	N	0.446260839	None	None	N
T/S	0.1012	likely_benign	0.0999	benign	-0.716	Destabilizing	0.062	N	0.232	neutral	N	0.37072293	None	None	N
T/V	0.1753	likely_benign	0.1723	benign	-0.64	Destabilizing	0.728	D	0.328	neutral	None	None	None	None	N
T/W	0.6993	likely_pathogenic	0.6844	pathogenic	-1.174	Destabilizing	0.998	D	0.542	neutral	None	None	None	None	N
T/Y	0.32	likely_benign	0.3304	benign	-0.938	Destabilizing	0.991	D	0.456	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.