TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26113	78562;78563;78564	chr2:178567795;178567794;178567793	chr2:179432522;179432521;179432520
N2AB	24472	73639;73640;73641	chr2:178567795;178567794;178567793	chr2:179432522;179432521;179432520
N2A	23545	70858;70859;70860	chr2:178567795;178567794;178567793	chr2:179432522;179432521;179432520
N2B	17048	51367;51368;51369	chr2:178567795;178567794;178567793	chr2:179432522;179432521;179432520
Novex-1	17173	51742;51743;51744	chr2:178567795;178567794;178567793	chr2:179432522;179432521;179432520
Novex-2	17240	51943;51944;51945	chr2:178567795;178567794;178567793	chr2:179432522;179432521;179432520
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: Fn3-78
• Domain position: 26
• Structural Position: 28
• Q(SASA): 0.4228
• 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/A	None	None	None	N	0.039	0.056	0.0762999501168	gnomAD-4.0.0	1.20033E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.31251E-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	0.0727	likely_benign	0.0705	benign	-0.408	Destabilizing	None	N	0.039	neutral	N	0.397112603	None	None	I
V/C	0.5406	ambiguous	0.5215	ambiguous	-0.621	Destabilizing	0.356	N	0.305	neutral	None	None	None	None	I
V/D	0.1817	likely_benign	0.1656	benign	-0.569	Destabilizing	0.016	N	0.338	neutral	None	None	None	None	I
V/E	0.1127	likely_benign	0.0933	benign	-0.686	Destabilizing	None	N	0.121	neutral	N	0.36561626	None	None	I
V/F	0.1459	likely_benign	0.1489	benign	-0.694	Destabilizing	0.214	N	0.389	neutral	None	None	None	None	I
V/G	0.1185	likely_benign	0.1118	benign	-0.512	Destabilizing	0.012	N	0.333	neutral	N	0.413660923	None	None	I
V/H	0.327	likely_benign	0.3193	benign	-0.069	Destabilizing	0.356	N	0.347	neutral	None	None	None	None	I
V/I	0.0671	likely_benign	0.0676	benign	-0.283	Destabilizing	None	N	0.072	neutral	None	None	None	None	I
V/K	0.1577	likely_benign	0.1396	benign	-0.49	Destabilizing	0.016	N	0.302	neutral	None	None	None	None	I
V/L	0.0984	likely_benign	0.0966	benign	-0.283	Destabilizing	0.005	N	0.095	neutral	N	0.412159413	None	None	I
V/M	0.0958	likely_benign	0.0937	benign	-0.46	Destabilizing	0.171	N	0.272	neutral	N	0.452256597	None	None	I
V/N	0.1254	likely_benign	0.1227	benign	-0.227	Destabilizing	0.072	N	0.471	neutral	None	None	None	None	I
V/P	0.2485	likely_benign	0.245	benign	-0.292	Destabilizing	0.072	N	0.449	neutral	None	None	None	None	I
V/Q	0.137	likely_benign	0.1215	benign	-0.484	Destabilizing	0.003	N	0.178	neutral	None	None	None	None	I
V/R	0.1782	likely_benign	0.1552	benign	0.054	Stabilizing	0.038	N	0.446	neutral	None	None	None	None	I
V/S	0.0934	likely_benign	0.0919	benign	-0.504	Destabilizing	0.016	N	0.275	neutral	None	None	None	None	I
V/T	0.0951	likely_benign	0.0925	benign	-0.53	Destabilizing	0.016	N	0.19	neutral	None	None	None	None	I
V/W	0.7046	likely_pathogenic	0.7028	pathogenic	-0.772	Destabilizing	0.864	D	0.327	neutral	None	None	None	None	I
V/Y	0.3817	ambiguous	0.3717	ambiguous	-0.487	Destabilizing	0.356	N	0.371	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.