TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8506	25741;25742;25743	chr2:178717218;178717217;178717216	chr2:179581945;179581944;179581943
N2AB	8189	24790;24791;24792	chr2:178717218;178717217;178717216	chr2:179581945;179581944;179581943
N2A	7262	22009;22010;22011	chr2:178717218;178717217;178717216	chr2:179581945;179581944;179581943
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: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Ig-70
• Domain position: 51
• Structural Position: 127
• Q(SASA): 0.4249
• 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
L/F	rs748617903	None	0.026	N	0.217	0.118	0.386234084001	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	0	0	None	0	2.75482E-04	None	0	0	1.3125E-06	0	0
L/V	None	None	0.452	N	0.498	0.092	0.243972157842	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
L/A	0.1998	likely_benign	0.2445	benign	-0.88	Destabilizing	0.966	D	0.525	neutral	None	None	None	None	I
L/C	0.5298	ambiguous	0.5978	pathogenic	-0.636	Destabilizing	0.17	N	0.369	neutral	None	None	None	None	I
L/D	0.6985	likely_pathogenic	0.7452	pathogenic	-0.352	Destabilizing	0.998	D	0.708	prob.delet.	None	None	None	None	I
L/E	0.3633	ambiguous	0.4242	ambiguous	-0.438	Destabilizing	0.998	D	0.711	prob.delet.	None	None	None	None	I
L/F	0.0828	likely_benign	0.0957	benign	-0.875	Destabilizing	0.026	N	0.217	neutral	N	0.386410899	None	None	I
L/G	0.5475	ambiguous	0.6235	pathogenic	-1.077	Destabilizing	0.995	D	0.679	prob.neutral	None	None	None	None	I
L/H	0.175	likely_benign	0.2072	benign	-0.425	Destabilizing	0.999	D	0.712	prob.delet.	None	None	None	None	I
L/I	0.081	likely_benign	0.0858	benign	-0.475	Destabilizing	0.294	N	0.475	neutral	None	None	None	None	I
L/K	0.3013	likely_benign	0.3589	ambiguous	-0.469	Destabilizing	0.947	D	0.7	prob.neutral	None	None	None	None	I
L/M	0.0889	likely_benign	0.0972	benign	-0.34	Destabilizing	0.948	D	0.561	neutral	N	0.499522974	None	None	I
L/N	0.3932	ambiguous	0.4365	ambiguous	-0.235	Destabilizing	0.998	D	0.712	prob.delet.	None	None	None	None	I
L/P	0.641	likely_pathogenic	0.7101	pathogenic	-0.576	Destabilizing	0.998	D	0.712	prob.delet.	None	None	None	None	I
L/Q	0.1476	likely_benign	0.1756	benign	-0.484	Destabilizing	0.996	D	0.697	prob.neutral	None	None	None	None	I
L/R	0.1908	likely_benign	0.2264	benign	0.103	Stabilizing	0.996	D	0.695	prob.neutral	None	None	None	None	I
L/S	0.2496	likely_benign	0.305	benign	-0.725	Destabilizing	0.993	D	0.643	neutral	N	0.452153101	None	None	I
L/T	0.1767	likely_benign	0.2073	benign	-0.699	Destabilizing	0.945	D	0.563	neutral	None	None	None	None	I
L/V	0.0723	likely_benign	0.0784	benign	-0.576	Destabilizing	0.452	N	0.498	neutral	N	0.439799879	None	None	I
L/W	0.169	likely_benign	0.1986	benign	-0.893	Destabilizing	1.0	D	0.705	prob.neutral	N	0.515588504	None	None	I
L/Y	0.2394	likely_benign	0.2732	benign	-0.632	Destabilizing	0.698	D	0.555	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.