TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22242	66949;66950;66951	chr2:178581544;178581543;178581542	chr2:179446271;179446270;179446269
N2AB	20601	62026;62027;62028	chr2:178581544;178581543;178581542	chr2:179446271;179446270;179446269
N2A	19674	59245;59246;59247	chr2:178581544;178581543;178581542	chr2:179446271;179446270;179446269
N2B	13177	39754;39755;39756	chr2:178581544;178581543;178581542	chr2:179446271;179446270;179446269
Novex-1	13302	40129;40130;40131	chr2:178581544;178581543;178581542	chr2:179446271;179446270;179446269
Novex-2	13369	40330;40331;40332	chr2:178581544;178581543;178581542	chr2:179446271;179446270;179446269
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Fn3-49
• Domain position: 87
• Structural Position: 119
• Q(SASA): 0.6813
• 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
D/H	None	None	0.99	N	0.624	0.343	0.264081493735	gnomAD-4.0.0	1.59891E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.87467E-06	0	0
D/N	None	None	0.904	N	0.632	0.275	0.221019684889	gnomAD-4.0.0	1.59891E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.87467E-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
D/A	0.2372	likely_benign	0.2574	benign	-0.492	Destabilizing	0.014	N	0.339	neutral	N	0.474477308	None	None	I
D/C	0.7986	likely_pathogenic	0.8357	pathogenic	-0.197	Destabilizing	0.994	D	0.677	prob.neutral	None	None	None	None	I
D/E	0.1302	likely_benign	0.1428	benign	-0.426	Destabilizing	0.025	N	0.119	neutral	N	0.361826593	None	None	I
D/F	0.7287	likely_pathogenic	0.7534	pathogenic	-0.194	Destabilizing	0.978	D	0.659	neutral	None	None	None	None	I
D/G	0.4167	ambiguous	0.4439	ambiguous	-0.731	Destabilizing	0.698	D	0.54	neutral	N	0.488945329	None	None	I
D/H	0.4789	ambiguous	0.5297	ambiguous	-0.021	Destabilizing	0.99	D	0.624	neutral	N	0.514670492	None	None	I
D/I	0.4444	ambiguous	0.4786	ambiguous	0.106	Stabilizing	0.956	D	0.631	neutral	None	None	None	None	I
D/K	0.4704	ambiguous	0.508	ambiguous	0.071	Stabilizing	0.86	D	0.564	neutral	None	None	None	None	I
D/L	0.4453	ambiguous	0.4696	ambiguous	0.106	Stabilizing	0.915	D	0.573	neutral	None	None	None	None	I
D/M	0.6634	likely_pathogenic	0.6997	pathogenic	0.259	Stabilizing	0.998	D	0.648	neutral	None	None	None	None	I
D/N	0.1965	likely_benign	0.2026	benign	-0.365	Destabilizing	0.904	D	0.632	neutral	N	0.507032444	None	None	I
D/P	0.6343	likely_pathogenic	0.6688	pathogenic	-0.071	Destabilizing	0.978	D	0.621	neutral	None	None	None	None	I
D/Q	0.379	ambiguous	0.4279	ambiguous	-0.296	Destabilizing	0.86	D	0.565	neutral	None	None	None	None	I
D/R	0.5531	ambiguous	0.6036	pathogenic	0.354	Stabilizing	0.956	D	0.587	neutral	None	None	None	None	I
D/S	0.2209	likely_benign	0.2283	benign	-0.486	Destabilizing	0.754	D	0.499	neutral	None	None	None	None	I
D/T	0.3521	ambiguous	0.3785	ambiguous	-0.29	Destabilizing	0.86	D	0.613	neutral	None	None	None	None	I
D/V	0.2706	likely_benign	0.2993	benign	-0.071	Destabilizing	0.698	D	0.597	neutral	N	0.493929861	None	None	I
D/W	0.9394	likely_pathogenic	0.9513	pathogenic	0.029	Stabilizing	0.998	D	0.753	deleterious	None	None	None	None	I
D/Y	0.3985	ambiguous	0.4317	ambiguous	0.062	Stabilizing	0.99	D	0.658	neutral	N	0.471622274	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.