TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5886	17881;17882;17883	chr2:178731009;178731008;178731007	chr2:179595736;179595735;179595734
N2AB	5569	16930;16931;16932	chr2:178731009;178731008;178731007	chr2:179595736;179595735;179595734
N2A	4642	14149;14150;14151	chr2:178731009;178731008;178731007	chr2:179595736;179595735;179595734
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: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-42
• Domain position: 64
• Structural Position: 145
• Q(SASA): 0.4305
• Predicted PPI site: N

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
E/D	None	None	0.02	N	0.178	0.146	0.220303561663	gnomAD-4.0.0	1.59168E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85894E-06	0	0
E/V	None	None	0.991	N	0.743	0.479	0.653813299475	gnomAD-4.0.0	1.59169E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85894E-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
E/A	0.1838	likely_benign	0.1972	benign	-0.677	Destabilizing	0.939	D	0.589	neutral	N	0.48942341	None	None	N
E/C	0.8508	likely_pathogenic	0.8866	pathogenic	-0.168	Destabilizing	0.999	D	0.82	deleterious	None	None	None	None	N
E/D	0.1113	likely_benign	0.1145	benign	-0.654	Destabilizing	0.02	N	0.178	neutral	N	0.422526414	None	None	N
E/F	0.8152	likely_pathogenic	0.8479	pathogenic	-0.427	Destabilizing	0.999	D	0.79	deleterious	None	None	None	None	N
E/G	0.1387	likely_benign	0.1695	benign	-0.945	Destabilizing	0.939	D	0.592	neutral	N	0.490290202	None	None	N
E/H	0.4879	ambiguous	0.5278	ambiguous	-0.468	Destabilizing	0.999	D	0.669	neutral	None	None	None	None	N
E/I	0.512	ambiguous	0.5464	ambiguous	0.022	Stabilizing	0.993	D	0.808	deleterious	None	None	None	None	N
E/K	0.1606	likely_benign	0.1945	benign	-0.047	Destabilizing	0.939	D	0.529	neutral	N	0.438917232	None	None	N
E/L	0.4429	ambiguous	0.4835	ambiguous	0.022	Stabilizing	0.993	D	0.775	deleterious	None	None	None	None	N
E/M	0.5122	ambiguous	0.5548	ambiguous	0.346	Stabilizing	0.999	D	0.753	deleterious	None	None	None	None	N
E/N	0.2287	likely_benign	0.253	benign	-0.439	Destabilizing	0.973	D	0.645	neutral	None	None	None	None	N
E/P	0.9082	likely_pathogenic	0.9329	pathogenic	-0.19	Destabilizing	0.993	D	0.719	prob.delet.	None	None	None	None	N
E/Q	0.1385	likely_benign	0.1469	benign	-0.375	Destabilizing	0.991	D	0.627	neutral	N	0.461620733	None	None	N
E/R	0.2699	likely_benign	0.3177	benign	0.165	Stabilizing	0.993	D	0.692	prob.neutral	None	None	None	None	N
E/S	0.2006	likely_benign	0.2176	benign	-0.649	Destabilizing	0.953	D	0.541	neutral	None	None	None	None	N
E/T	0.2408	likely_benign	0.2694	benign	-0.43	Destabilizing	0.993	D	0.661	neutral	None	None	None	None	N
E/V	0.2861	likely_benign	0.3157	benign	-0.19	Destabilizing	0.991	D	0.743	deleterious	N	0.490636918	None	None	N
E/W	0.9044	likely_pathogenic	0.9253	pathogenic	-0.218	Destabilizing	0.999	D	0.817	deleterious	None	None	None	None	N
E/Y	0.6935	likely_pathogenic	0.75	pathogenic	-0.178	Destabilizing	0.999	D	0.767	deleterious	None	None	None	None	N

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.