TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31862	95809;95810;95811	chr2:178545526;178545525;178545524	chr2:179410253;179410252;179410251
N2AB	30221	90886;90887;90888	chr2:178545526;178545525;178545524	chr2:179410253;179410252;179410251
N2A	29294	88105;88106;88107	chr2:178545526;178545525;178545524	chr2:179410253;179410252;179410251
N2B	22797	68614;68615;68616	chr2:178545526;178545525;178545524	chr2:179410253;179410252;179410251
Novex-1	22922	68989;68990;68991	chr2:178545526;178545525;178545524	chr2:179410253;179410252;179410251
Novex-2	22989	69190;69191;69192	chr2:178545526;178545525;178545524	chr2:179410253;179410252;179410251
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Fn3-120
• Domain position: 56
• Structural Position: 75
• Q(SASA): 0.3939
• 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/A	None	None	0.09	N	0.212	0.15	0.469333501611	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.0878	likely_benign	0.1027	benign	-0.973	Destabilizing	0.09	N	0.212	neutral	N	0.398672828	None	None	N
V/C	0.4096	ambiguous	0.4752	ambiguous	-0.559	Destabilizing	0.944	D	0.256	neutral	None	None	None	None	N
V/D	0.2718	likely_benign	0.2674	benign	-0.181	Destabilizing	0.388	N	0.364	neutral	None	None	None	None	N
V/E	0.2148	likely_benign	0.2237	benign	-0.182	Destabilizing	0.324	N	0.31	neutral	N	0.420490895	None	None	N
V/F	0.1422	likely_benign	0.1507	benign	-0.703	Destabilizing	0.818	D	0.316	neutral	None	None	None	None	N
V/G	0.1562	likely_benign	0.1691	benign	-1.253	Destabilizing	0.324	N	0.326	neutral	N	0.436807142	None	None	N
V/H	0.3143	likely_benign	0.3618	ambiguous	-0.606	Destabilizing	0.981	D	0.317	neutral	None	None	None	None	N
V/I	0.0618	likely_benign	0.0665	benign	-0.324	Destabilizing	0.008	N	0.094	neutral	None	None	None	None	N
V/K	0.1881	likely_benign	0.2136	benign	-0.529	Destabilizing	0.388	N	0.305	neutral	None	None	None	None	N
V/L	0.1008	likely_benign	0.1164	benign	-0.324	Destabilizing	0.041	N	0.171	neutral	N	0.353017896	None	None	N
V/M	0.0823	likely_benign	0.0956	benign	-0.357	Destabilizing	0.773	D	0.329	neutral	N	0.46686069	None	None	N
V/N	0.1346	likely_benign	0.1553	benign	-0.367	Destabilizing	0.69	D	0.366	neutral	None	None	None	None	N
V/P	0.1793	likely_benign	0.2172	benign	-0.505	Destabilizing	0.818	D	0.346	neutral	None	None	None	None	N
V/Q	0.1891	likely_benign	0.2148	benign	-0.48	Destabilizing	0.818	D	0.334	neutral	None	None	None	None	N
V/R	0.1758	likely_benign	0.1999	benign	-0.112	Destabilizing	0.69	D	0.375	neutral	None	None	None	None	N
V/S	0.1089	likely_benign	0.1224	benign	-0.935	Destabilizing	0.116	N	0.267	neutral	None	None	None	None	N
V/T	0.0713	likely_benign	0.0843	benign	-0.816	Destabilizing	None	N	0.08	neutral	None	None	None	None	N
V/W	0.5906	likely_pathogenic	0.6472	pathogenic	-0.847	Destabilizing	0.981	D	0.351	neutral	None	None	None	None	N
V/Y	0.3512	ambiguous	0.389	ambiguous	-0.525	Destabilizing	0.818	D	0.299	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.