TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19103	57532;57533;57534	chr2:178597775;178597774;178597773	chr2:179462502;179462501;179462500
N2AB	17462	52609;52610;52611	chr2:178597775;178597774;178597773	chr2:179462502;179462501;179462500
N2A	16535	49828;49829;49830	chr2:178597775;178597774;178597773	chr2:179462502;179462501;179462500
N2B	10038	30337;30338;30339	chr2:178597775;178597774;178597773	chr2:179462502;179462501;179462500
Novex-1	10163	30712;30713;30714	chr2:178597775;178597774;178597773	chr2:179462502;179462501;179462500
Novex-2	10230	30913;30914;30915	chr2:178597775;178597774;178597773	chr2:179462502;179462501;179462500
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-117
• Domain position: 9
• Structural Position: 14
• Q(SASA): 0.6005
• 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	0.998	N	0.496	0.402	0.722099309044	gnomAD-4.0.0	4.80129E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.25001E-06	0	0
V/I	None	None	0.767	D	0.307	0.262	0.547212138244	gnomAD-4.0.0	4.10669E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.3978E-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	0.3232	likely_benign	0.3695	ambiguous	-1.199	Destabilizing	0.998	D	0.496	neutral	N	0.493467917	None	None	I
V/C	0.8525	likely_pathogenic	0.8445	pathogenic	-0.768	Destabilizing	1.0	D	0.647	neutral	None	None	None	None	I
V/D	0.7983	likely_pathogenic	0.837	pathogenic	-1.004	Destabilizing	1.0	D	0.723	prob.delet.	N	0.504205566	None	None	I
V/E	0.6204	likely_pathogenic	0.6728	pathogenic	-1.018	Destabilizing	1.0	D	0.686	prob.neutral	None	None	None	None	I
V/F	0.3864	ambiguous	0.4374	ambiguous	-0.903	Destabilizing	0.999	D	0.697	prob.neutral	N	0.51657583	None	None	I
V/G	0.568	likely_pathogenic	0.6454	pathogenic	-1.486	Destabilizing	1.0	D	0.711	prob.delet.	D	0.52758974	None	None	I
V/H	0.7931	likely_pathogenic	0.824	pathogenic	-0.967	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	I
V/I	0.0848	likely_benign	0.0836	benign	-0.525	Destabilizing	0.767	D	0.307	neutral	D	0.526653647	None	None	I
V/K	0.6364	likely_pathogenic	0.6936	pathogenic	-1.107	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	I
V/L	0.3281	likely_benign	0.3685	ambiguous	-0.525	Destabilizing	0.981	D	0.473	neutral	N	0.489317315	None	None	I
V/M	0.2251	likely_benign	0.2483	benign	-0.435	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	I
V/N	0.5483	ambiguous	0.5885	pathogenic	-0.866	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	I
V/P	0.901	likely_pathogenic	0.9179	pathogenic	-0.714	Destabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	I
V/Q	0.5427	ambiguous	0.574	pathogenic	-1.029	Destabilizing	1.0	D	0.692	prob.neutral	None	None	None	None	I
V/R	0.5732	likely_pathogenic	0.6386	pathogenic	-0.564	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	I
V/S	0.4008	ambiguous	0.4357	ambiguous	-1.332	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	I
V/T	0.1839	likely_benign	0.1832	benign	-1.238	Destabilizing	0.998	D	0.666	neutral	None	None	None	None	I
V/W	0.9407	likely_pathogenic	0.9527	pathogenic	-1.08	Destabilizing	1.0	D	0.716	prob.delet.	None	None	None	None	I
V/Y	0.8167	likely_pathogenic	0.8349	pathogenic	-0.797	Destabilizing	1.0	D	0.703	prob.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.