TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5411	16456;16457;16458	chr2:178732945;178732944;178732943	chr2:179597672;179597671;179597670
N2AB	5094	15505;15506;15507	chr2:178732945;178732944;178732943	chr2:179597672;179597671;179597670
N2A	4167	12724;12725;12726	chr2:178732945;178732944;178732943	chr2:179597672;179597671;179597670
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: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-37
• Domain position: 55
• Structural Position: 135
• Q(SASA): 0.2266
• 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
T/I	rs757542282	-0.135	0.669	N	0.525	0.312	0.53782465974	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
T/I	rs757542282	-0.135	0.669	N	0.525	0.312	0.53782465974	gnomAD-4.0.0	1.36862E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79899E-06	0	0
T/P	None	None	0.966	D	0.549	0.451	0.586114214298	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05

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
T/A	0.0896	likely_benign	0.0858	benign	-1.025	Destabilizing	0.454	N	0.429	neutral	N	0.496906743	None	None	N
T/C	0.4696	ambiguous	0.4375	ambiguous	-0.667	Destabilizing	0.998	D	0.515	neutral	None	None	None	None	N
T/D	0.4953	ambiguous	0.4452	ambiguous	-0.555	Destabilizing	0.842	D	0.53	neutral	None	None	None	None	N
T/E	0.4036	ambiguous	0.3741	ambiguous	-0.517	Destabilizing	0.842	D	0.527	neutral	None	None	None	None	N
T/F	0.2198	likely_benign	0.2008	benign	-0.994	Destabilizing	0.949	D	0.581	neutral	None	None	None	None	N
T/G	0.2885	likely_benign	0.2841	benign	-1.319	Destabilizing	0.728	D	0.518	neutral	None	None	None	None	N
T/H	0.3005	likely_benign	0.2719	benign	-1.587	Destabilizing	0.998	D	0.554	neutral	None	None	None	None	N
T/I	0.1694	likely_benign	0.1527	benign	-0.317	Destabilizing	0.669	D	0.525	neutral	N	0.47941706	None	None	N
T/K	0.2836	likely_benign	0.2556	benign	-0.815	Destabilizing	0.801	D	0.501	neutral	N	0.491634209	None	None	N
T/L	0.1237	likely_benign	0.1133	benign	-0.317	Destabilizing	0.016	N	0.263	neutral	None	None	None	None	N
T/M	0.0931	likely_benign	0.0861	benign	0.004	Stabilizing	0.949	D	0.542	neutral	None	None	None	None	N
T/N	0.1281	likely_benign	0.118	benign	-0.872	Destabilizing	0.842	D	0.498	neutral	None	None	None	None	N
T/P	0.4739	ambiguous	0.4329	ambiguous	-0.521	Destabilizing	0.966	D	0.549	neutral	D	0.52434406	None	None	N
T/Q	0.2744	likely_benign	0.258	benign	-1.01	Destabilizing	0.974	D	0.562	neutral	None	None	None	None	N
T/R	0.2247	likely_benign	0.2017	benign	-0.636	Destabilizing	0.934	D	0.55	neutral	N	0.481129214	None	None	N
T/S	0.1099	likely_benign	0.1043	benign	-1.166	Destabilizing	0.022	N	0.16	neutral	N	0.429681673	None	None	N
T/V	0.1384	likely_benign	0.1295	benign	-0.521	Destabilizing	0.728	D	0.461	neutral	None	None	None	None	N
T/W	0.6045	likely_pathogenic	0.572	pathogenic	-0.92	Destabilizing	0.998	D	0.59	neutral	None	None	None	None	N
T/Y	0.289	likely_benign	0.2644	benign	-0.683	Destabilizing	0.991	D	0.596	neutral	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.