TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21986	66181;66182;66183	chr2:178582500;178582499;178582498	chr2:179447227;179447226;179447225
N2AB	20345	61258;61259;61260	chr2:178582500;178582499;178582498	chr2:179447227;179447226;179447225
N2A	19418	58477;58478;58479	chr2:178582500;178582499;178582498	chr2:179447227;179447226;179447225
N2B	12921	38986;38987;38988	chr2:178582500;178582499;178582498	chr2:179447227;179447226;179447225
Novex-1	13046	39361;39362;39363	chr2:178582500;178582499;178582498	chr2:179447227;179447226;179447225
Novex-2	13113	39562;39563;39564	chr2:178582500;178582499;178582498	chr2:179447227;179447226;179447225
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Fn3-47
• Domain position: 31
• Structural Position: 33
• Q(SASA): 0.1675
• 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
S/P	rs1170003837	None	0.994	D	0.705	0.395	0.464698922459	gnomAD-4.0.0	1.59315E-06	None	None	None	None	I	None	0	2.28822E-05	None	0	0	None	0	0	0	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
S/A	0.1228	likely_benign	0.1253	benign	-0.835	Destabilizing	0.63	D	0.58	neutral	N	0.487966681	None	None	I
S/C	0.1612	likely_benign	0.1354	benign	-0.546	Destabilizing	0.073	N	0.587	neutral	None	None	None	None	I
S/D	0.8673	likely_pathogenic	0.8108	pathogenic	-0.469	Destabilizing	0.996	D	0.711	prob.delet.	None	None	None	None	I
S/E	0.9371	likely_pathogenic	0.9161	pathogenic	-0.47	Destabilizing	0.996	D	0.714	prob.delet.	None	None	None	None	I
S/F	0.7508	likely_pathogenic	0.7207	pathogenic	-1.043	Destabilizing	0.987	D	0.716	prob.delet.	None	None	None	None	I
S/G	0.3281	likely_benign	0.286	benign	-1.085	Destabilizing	0.957	D	0.606	neutral	None	None	None	None	I
S/H	0.8675	likely_pathogenic	0.8076	pathogenic	-1.587	Destabilizing	0.999	D	0.694	prob.neutral	None	None	None	None	I
S/I	0.8216	likely_pathogenic	0.7699	pathogenic	-0.275	Destabilizing	0.975	D	0.726	prob.delet.	None	None	None	None	I
S/K	0.9902	likely_pathogenic	0.9848	pathogenic	-0.812	Destabilizing	0.987	D	0.703	prob.neutral	None	None	None	None	I
S/L	0.4561	ambiguous	0.3917	ambiguous	-0.275	Destabilizing	0.805	D	0.671	neutral	N	0.491033657	None	None	I
S/M	0.5747	likely_pathogenic	0.5181	ambiguous	0.106	Stabilizing	0.999	D	0.691	prob.neutral	None	None	None	None	I
S/N	0.6275	likely_pathogenic	0.555	ambiguous	-0.782	Destabilizing	0.996	D	0.719	prob.delet.	None	None	None	None	I
S/P	0.994	likely_pathogenic	0.9931	pathogenic	-0.429	Destabilizing	0.994	D	0.705	prob.neutral	D	0.539928372	None	None	I
S/Q	0.9235	likely_pathogenic	0.8975	pathogenic	-0.948	Destabilizing	0.996	D	0.713	prob.delet.	None	None	None	None	I
S/R	0.9826	likely_pathogenic	0.9726	pathogenic	-0.695	Destabilizing	0.996	D	0.695	prob.neutral	None	None	None	None	I
S/T	0.3524	ambiguous	0.3033	benign	-0.781	Destabilizing	0.892	D	0.621	neutral	N	0.482702318	None	None	I
S/V	0.7031	likely_pathogenic	0.6401	pathogenic	-0.429	Destabilizing	0.975	D	0.705	prob.neutral	None	None	None	None	I
S/W	0.8614	likely_pathogenic	0.8207	pathogenic	-1.01	Destabilizing	0.999	D	0.745	deleterious	None	None	None	None	I
S/Y	0.7337	likely_pathogenic	0.6827	pathogenic	-0.756	Destabilizing	0.996	D	0.716	prob.delet.	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.