TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28927	87004;87005;87006	chr2:178559353;178559352;178559351	chr2:179424080;179424079;179424078
N2AB	27286	82081;82082;82083	chr2:178559353;178559352;178559351	chr2:179424080;179424079;179424078
N2A	26359	79300;79301;79302	chr2:178559353;178559352;178559351	chr2:179424080;179424079;179424078
N2B	19862	59809;59810;59811	chr2:178559353;178559352;178559351	chr2:179424080;179424079;179424078
Novex-1	19987	60184;60185;60186	chr2:178559353;178559352;178559351	chr2:179424080;179424079;179424078
Novex-2	20054	60385;60386;60387	chr2:178559353;178559352;178559351	chr2:179424080;179424079;179424078
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-98
• Domain position: 83
• Structural Position: 117
• Q(SASA): 0.4187
• 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
V/I	None	None	None	N	0.197	0.056	0.139678290688	gnomAD-4.0.0	3.60098E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.93752E-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
V/A	0.105	likely_benign	0.1146	benign	-0.928	Destabilizing	0.052	N	0.481	neutral	N	0.449042933	None	None	N
V/C	0.572	likely_pathogenic	0.6067	pathogenic	-0.794	Destabilizing	0.935	D	0.576	neutral	None	None	None	None	N
V/D	0.36	ambiguous	0.4195	ambiguous	-0.931	Destabilizing	0.484	N	0.635	neutral	N	0.486657172	None	None	N
V/E	0.2642	likely_benign	0.2996	benign	-1.038	Destabilizing	0.38	N	0.629	neutral	None	None	None	None	N
V/F	0.158	likely_benign	0.163	benign	-1.222	Destabilizing	0.317	N	0.602	neutral	N	0.518788233	None	None	N
V/G	0.1989	likely_benign	0.2208	benign	-1.087	Destabilizing	0.117	N	0.619	neutral	N	0.50670437	None	None	N
V/H	0.4913	ambiguous	0.53	ambiguous	-0.596	Destabilizing	0.935	D	0.636	neutral	None	None	None	None	N
V/I	0.062	likely_benign	0.0605	benign	-0.641	Destabilizing	None	N	0.197	neutral	N	0.415277076	None	None	N
V/K	0.2989	likely_benign	0.3096	benign	-0.563	Destabilizing	0.38	N	0.629	neutral	None	None	None	None	N
V/L	0.1356	likely_benign	0.1371	benign	-0.641	Destabilizing	0.009	N	0.407	neutral	N	0.449773652	None	None	N
V/M	0.1089	likely_benign	0.1033	benign	-0.392	Destabilizing	0.38	N	0.593	neutral	None	None	None	None	N
V/N	0.2404	likely_benign	0.2747	benign	-0.332	Destabilizing	0.555	D	0.648	neutral	None	None	None	None	N
V/P	0.2892	likely_benign	0.3138	benign	-0.702	Destabilizing	0.001	N	0.469	neutral	None	None	None	None	N
V/Q	0.2838	likely_benign	0.2993	benign	-0.686	Destabilizing	0.555	D	0.648	neutral	None	None	None	None	N
V/R	0.2607	likely_benign	0.2759	benign	0.04	Stabilizing	0.555	D	0.646	neutral	None	None	None	None	N
V/S	0.1681	likely_benign	0.1879	benign	-0.724	Destabilizing	0.081	N	0.618	neutral	None	None	None	None	N
V/T	0.1075	likely_benign	0.1098	benign	-0.737	Destabilizing	0.002	N	0.313	neutral	None	None	None	None	N
V/W	0.6812	likely_pathogenic	0.7022	pathogenic	-1.248	Destabilizing	0.935	D	0.673	neutral	None	None	None	None	N
V/Y	0.4665	ambiguous	0.5001	ambiguous	-0.928	Destabilizing	0.555	D	0.592	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.