TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6231	18916;18917;18918	chr2:178729465;178729464;178729463	chr2:179594192;179594191;179594190
N2AB	5914	17965;17966;17967	chr2:178729465;178729464;178729463	chr2:179594192;179594191;179594190
N2A	4987	15184;15185;15186	chr2:178729465;178729464;178729463	chr2:179594192;179594191;179594190
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: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-46
• Domain position: 33
• Structural Position: 47
• Q(SASA): 0.2498
• 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/A	None	None	0.174	N	0.523	0.26	0.252681307341	gnomAD-4.0.0	1.36857E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79913E-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	0.0864	likely_benign	0.0917	benign	-0.747	Destabilizing	0.174	N	0.523	neutral	N	0.502924892	None	None	N
T/C	0.4107	ambiguous	0.4761	ambiguous	-0.447	Destabilizing	0.991	D	0.657	neutral	None	None	None	None	N
T/D	0.4148	ambiguous	0.4511	ambiguous	-0.324	Destabilizing	0.826	D	0.65	neutral	None	None	None	None	N
T/E	0.3044	likely_benign	0.3385	benign	-0.26	Destabilizing	0.404	N	0.609	neutral	None	None	None	None	N
T/F	0.1794	likely_benign	0.2021	benign	-0.556	Destabilizing	0.826	D	0.727	prob.delet.	None	None	None	None	N
T/G	0.2564	likely_benign	0.2768	benign	-1.074	Destabilizing	0.575	D	0.659	neutral	None	None	None	None	N
T/H	0.1686	likely_benign	0.1971	benign	-1.275	Destabilizing	0.991	D	0.723	prob.delet.	None	None	None	None	N
T/I	0.1243	likely_benign	0.1464	benign	0.054	Stabilizing	0.007	N	0.395	neutral	N	0.49227983	None	None	N
T/K	0.1364	likely_benign	0.1501	benign	-0.765	Destabilizing	0.01	N	0.397	neutral	None	None	None	None	N
T/L	0.0825	likely_benign	0.0916	benign	0.054	Stabilizing	0.189	N	0.579	neutral	None	None	None	None	N
T/M	0.0788	likely_benign	0.0824	benign	0.119	Stabilizing	0.947	D	0.665	neutral	None	None	None	None	N
T/N	0.1122	likely_benign	0.124	benign	-0.847	Destabilizing	0.782	D	0.568	neutral	N	0.497355485	None	None	N
T/P	0.5838	likely_pathogenic	0.5822	pathogenic	-0.179	Destabilizing	0.879	D	0.681	prob.neutral	D	0.545680769	None	None	N
T/Q	0.1688	likely_benign	0.1857	benign	-0.828	Destabilizing	0.826	D	0.668	neutral	None	None	None	None	N
T/R	0.1077	likely_benign	0.1142	benign	-0.676	Destabilizing	0.704	D	0.652	neutral	None	None	None	None	N
T/S	0.0992	likely_benign	0.1081	benign	-1.102	Destabilizing	0.038	N	0.401	neutral	N	0.486070887	None	None	N
T/V	0.117	likely_benign	0.1382	benign	-0.179	Destabilizing	0.189	N	0.533	neutral	None	None	None	None	N
T/W	0.4598	ambiguous	0.4864	ambiguous	-0.6	Destabilizing	0.991	D	0.729	prob.delet.	None	None	None	None	N
T/Y	0.2242	likely_benign	0.2505	benign	-0.339	Destabilizing	0.906	D	0.739	prob.delet.	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.