TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24511	73756;73757;73758	chr2:178572601;178572600;178572599	chr2:179437328;179437327;179437326
N2AB	22870	68833;68834;68835	chr2:178572601;178572600;178572599	chr2:179437328;179437327;179437326
N2A	21943	66052;66053;66054	chr2:178572601;178572600;178572599	chr2:179437328;179437327;179437326
N2B	15446	46561;46562;46563	chr2:178572601;178572600;178572599	chr2:179437328;179437327;179437326
Novex-1	15571	46936;46937;46938	chr2:178572601;178572600;178572599	chr2:179437328;179437327;179437326
Novex-2	15638	47137;47138;47139	chr2:178572601;178572600;178572599	chr2:179437328;179437327;179437326
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Ig-132
• Domain position: 81
• Structural Position: 171
• Q(SASA): 0.5209
• 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
F/Y	rs1421171705	-0.012	0.981	D	0.615	0.198	0.538050722575	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
F/Y	rs1421171705	-0.012	0.981	D	0.615	0.198	0.538050722575	gnomAD-4.0.0	1.59222E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43373E-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
F/A	0.6123	likely_pathogenic	0.6194	pathogenic	-1.371	Destabilizing	0.845	D	0.657	neutral	None	None	None	None	I
F/C	0.538	ambiguous	0.5528	ambiguous	-0.51	Destabilizing	0.999	D	0.769	deleterious	N	0.512849166	None	None	I
F/D	0.9374	likely_pathogenic	0.9382	pathogenic	0.173	Stabilizing	0.975	D	0.768	deleterious	None	None	None	None	I
F/E	0.9444	likely_pathogenic	0.945	pathogenic	0.172	Stabilizing	0.975	D	0.758	deleterious	None	None	None	None	I
F/G	0.8904	likely_pathogenic	0.8984	pathogenic	-1.607	Destabilizing	0.845	D	0.716	prob.delet.	None	None	None	None	I
F/H	0.714	likely_pathogenic	0.746	pathogenic	-0.038	Destabilizing	0.999	D	0.709	prob.delet.	None	None	None	None	I
F/I	0.4073	ambiguous	0.4244	ambiguous	-0.731	Destabilizing	0.983	D	0.683	prob.neutral	N	0.493730953	None	None	I
F/K	0.9521	likely_pathogenic	0.9536	pathogenic	-0.481	Destabilizing	0.975	D	0.766	deleterious	None	None	None	None	I
F/L	0.9384	likely_pathogenic	0.938	pathogenic	-0.731	Destabilizing	0.892	D	0.634	neutral	D	0.526938861	None	None	I
F/M	0.6091	likely_pathogenic	0.6117	pathogenic	-0.563	Destabilizing	0.996	D	0.701	prob.neutral	None	None	None	None	I
F/N	0.731	likely_pathogenic	0.7429	pathogenic	-0.442	Destabilizing	0.975	D	0.78	deleterious	None	None	None	None	I
F/P	0.988	likely_pathogenic	0.9886	pathogenic	-0.928	Destabilizing	0.987	D	0.786	deleterious	None	None	None	None	I
F/Q	0.8883	likely_pathogenic	0.8917	pathogenic	-0.534	Destabilizing	0.975	D	0.785	deleterious	None	None	None	None	I
F/R	0.9158	likely_pathogenic	0.9117	pathogenic	0.107	Stabilizing	0.975	D	0.782	deleterious	None	None	None	None	I
F/S	0.4277	ambiguous	0.4474	ambiguous	-1.127	Destabilizing	0.204	N	0.557	neutral	N	0.452958391	None	None	I
F/T	0.3936	ambiguous	0.4152	ambiguous	-1.035	Destabilizing	0.845	D	0.699	prob.neutral	None	None	None	None	I
F/V	0.3164	likely_benign	0.3297	benign	-0.928	Destabilizing	0.892	D	0.699	prob.neutral	N	0.482374647	None	None	I
F/W	0.6701	likely_pathogenic	0.6927	pathogenic	-0.354	Destabilizing	0.999	D	0.685	prob.neutral	None	None	None	None	I
F/Y	0.2509	likely_benign	0.284	benign	-0.423	Destabilizing	0.981	D	0.615	neutral	D	0.530517884	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.