TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28975	87148;87149;87150	chr2:178558536;178558535;178558534	chr2:179423263;179423262;179423261
N2AB	27334	82225;82226;82227	chr2:178558536;178558535;178558534	chr2:179423263;179423262;179423261
N2A	26407	79444;79445;79446	chr2:178558536;178558535;178558534	chr2:179423263;179423262;179423261
N2B	19910	59953;59954;59955	chr2:178558536;178558535;178558534	chr2:179423263;179423262;179423261
Novex-1	20035	60328;60329;60330	chr2:178558536;178558535;178558534	chr2:179423263;179423262;179423261
Novex-2	20102	60529;60530;60531	chr2:178558536;178558535;178558534	chr2:179423263;179423262;179423261
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Fn3-99
• Domain position: 34
• Structural Position: 36
• Q(SASA): 0.2026
• Predicted PPI site: I

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/L	None	None	None	N	0.098	0.094	0.326345978581	gnomAD-4.0.0	1.59137E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43283E-05	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	0.1043	likely_benign	0.1119	benign	-1.215	Destabilizing	0.005	N	0.237	neutral	N	0.462761592	None	None	I
V/C	0.4892	ambiguous	0.5128	ambiguous	-0.578	Destabilizing	0.628	D	0.373	neutral	None	None	None	None	I
V/D	0.25	likely_benign	0.3066	benign	-1.285	Destabilizing	0.038	N	0.373	neutral	None	None	None	None	I
V/E	0.1848	likely_benign	0.2509	benign	-1.346	Destabilizing	None	N	0.197	neutral	N	0.440596808	None	None	I
V/F	0.1093	likely_benign	0.1164	benign	-1.1	Destabilizing	0.038	N	0.405	neutral	None	None	None	None	I
V/G	0.1207	likely_benign	0.1295	benign	-1.454	Destabilizing	None	N	0.189	neutral	N	0.452931387	None	None	I
V/H	0.3263	likely_benign	0.3604	ambiguous	-1.065	Destabilizing	0.356	N	0.427	neutral	None	None	None	None	I
V/I	0.0614	likely_benign	0.0618	benign	-0.678	Destabilizing	None	N	0.112	neutral	N	0.407793743	None	None	I
V/K	0.219	likely_benign	0.2767	benign	-1.115	Destabilizing	0.038	N	0.318	neutral	None	None	None	None	I
V/L	0.0896	likely_benign	0.0902	benign	-0.678	Destabilizing	None	N	0.098	neutral	N	0.374622532	None	None	I
V/M	0.0848	likely_benign	0.088	benign	-0.408	Destabilizing	0.007	N	0.249	neutral	None	None	None	None	I
V/N	0.129	likely_benign	0.1404	benign	-0.728	Destabilizing	0.072	N	0.413	neutral	None	None	None	None	I
V/P	0.6366	likely_pathogenic	0.6525	pathogenic	-0.823	Destabilizing	0.136	N	0.395	neutral	None	None	None	None	I
V/Q	0.183	likely_benign	0.2127	benign	-0.983	Destabilizing	0.038	N	0.428	neutral	None	None	None	None	I
V/R	0.1987	likely_benign	0.2561	benign	-0.494	Destabilizing	0.072	N	0.413	neutral	None	None	None	None	I
V/S	0.0984	likely_benign	0.104	benign	-1.083	Destabilizing	0.016	N	0.319	neutral	None	None	None	None	I
V/T	0.0849	likely_benign	0.0863	benign	-1.056	Destabilizing	None	N	0.069	neutral	None	None	None	None	I
V/W	0.605	likely_pathogenic	0.6592	pathogenic	-1.251	Destabilizing	0.864	D	0.421	neutral	None	None	None	None	I
V/Y	0.3517	ambiguous	0.3754	ambiguous	-1.0	Destabilizing	0.356	N	0.395	neutral	None	None	None	None	I

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.