TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8527	25804;25805;25806	chr2:178717155;178717154;178717153	chr2:179581882;179581881;179581880
N2AB	8210	24853;24854;24855	chr2:178717155;178717154;178717153	chr2:179581882;179581881;179581880
N2A	7283	22072;22073;22074	chr2:178717155;178717154;178717153	chr2:179581882;179581881;179581880
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: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-70
• Domain position: 72
• Structural Position: 155
• Q(SASA): 0.2694
• 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	rs1560626573	None	0.793	N	0.367	0.321	0.484763619824	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
T/I	rs1560626573	None	0.793	N	0.367	0.321	0.484763619824	gnomAD-4.0.0	2.7373E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.59837E-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	0.1063	likely_benign	0.1018	benign	-1.119	Destabilizing	0.943	D	0.444	neutral	N	0.497691203	None	None	N
T/C	0.4973	ambiguous	0.4918	ambiguous	-0.828	Destabilizing	1.0	D	0.49	neutral	None	None	None	None	N
T/D	0.5789	likely_pathogenic	0.5826	pathogenic	-1.75	Destabilizing	0.996	D	0.491	neutral	None	None	None	None	N
T/E	0.5014	ambiguous	0.4998	ambiguous	-1.536	Destabilizing	1.0	D	0.448	neutral	None	None	None	None	N
T/F	0.245	likely_benign	0.2458	benign	-0.795	Destabilizing	0.931	D	0.491	neutral	None	None	None	None	N
T/G	0.3781	ambiguous	0.3744	ambiguous	-1.527	Destabilizing	0.998	D	0.505	neutral	None	None	None	None	N
T/H	0.2839	likely_benign	0.2758	benign	-1.654	Destabilizing	0.999	D	0.58	neutral	None	None	None	None	N
T/I	0.1329	likely_benign	0.1367	benign	-0.042	Destabilizing	0.793	D	0.367	neutral	N	0.464761149	None	None	N
T/K	0.3317	likely_benign	0.3255	benign	-0.363	Destabilizing	1.0	D	0.43	neutral	None	None	None	None	N
T/L	0.1149	likely_benign	0.1175	benign	-0.042	Destabilizing	0.997	D	0.45	neutral	None	None	None	None	N
T/M	0.1042	likely_benign	0.1062	benign	-0.073	Destabilizing	1.0	D	0.505	neutral	None	None	None	None	N
T/N	0.173	likely_benign	0.1731	benign	-1.155	Destabilizing	0.994	D	0.447	neutral	N	0.507098952	None	None	N
T/P	0.7815	likely_pathogenic	0.7999	pathogenic	-0.372	Destabilizing	0.998	D	0.504	neutral	D	0.525456697	None	None	N
T/Q	0.3005	likely_benign	0.2927	benign	-0.905	Destabilizing	0.996	D	0.501	neutral	None	None	None	None	N
T/R	0.2281	likely_benign	0.2281	benign	-0.66	Destabilizing	0.974	D	0.368	neutral	None	None	None	None	N
T/S	0.1166	likely_benign	0.1144	benign	-1.323	Destabilizing	0.94	D	0.469	neutral	N	0.496884447	None	None	N
T/V	0.1196	likely_benign	0.1223	benign	-0.372	Destabilizing	0.982	D	0.445	neutral	None	None	None	None	N
T/W	0.6543	likely_pathogenic	0.6481	pathogenic	-1.013	Destabilizing	1.0	D	0.593	neutral	None	None	None	None	N
T/Y	0.3115	likely_benign	0.3026	benign	-0.605	Destabilizing	0.999	D	0.565	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.