TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31023	93292;93293;93294	chr2:178548559;178548558;178548557	chr2:179413286;179413285;179413284
N2AB	29382	88369;88370;88371	chr2:178548559;178548558;178548557	chr2:179413286;179413285;179413284
N2A	28455	85588;85589;85590	chr2:178548559;178548558;178548557	chr2:179413286;179413285;179413284
N2B	21958	66097;66098;66099	chr2:178548559;178548558;178548557	chr2:179413286;179413285;179413284
Novex-1	22083	66472;66473;66474	chr2:178548559;178548558;178548557	chr2:179413286;179413285;179413284
Novex-2	22150	66673;66674;66675	chr2:178548559;178548558;178548557	chr2:179413286;179413285;179413284
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-114
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.1073
• 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
I/F	None	None	0.976	N	0.711	0.301	0.387366425376	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	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
I/A	0.8413	likely_pathogenic	0.7695	pathogenic	-2.202	Highly Destabilizing	0.17	N	0.435	neutral	None	None	None	None	N
I/C	0.8919	likely_pathogenic	0.8636	pathogenic	-1.326	Destabilizing	0.999	D	0.677	prob.neutral	None	None	None	None	N
I/D	0.9968	likely_pathogenic	0.9934	pathogenic	-2.891	Highly Destabilizing	0.991	D	0.785	deleterious	None	None	None	None	N
I/E	0.9929	likely_pathogenic	0.9861	pathogenic	-2.606	Highly Destabilizing	0.991	D	0.767	deleterious	None	None	None	None	N
I/F	0.4284	ambiguous	0.3406	ambiguous	-1.264	Destabilizing	0.976	D	0.711	prob.delet.	N	0.492929783	None	None	N
I/G	0.9789	likely_pathogenic	0.9634	pathogenic	-2.775	Highly Destabilizing	0.982	D	0.754	deleterious	None	None	None	None	N
I/H	0.9859	likely_pathogenic	0.9746	pathogenic	-2.47	Highly Destabilizing	0.999	D	0.768	deleterious	None	None	None	None	N
I/K	0.9856	likely_pathogenic	0.9748	pathogenic	-1.672	Destabilizing	0.991	D	0.763	deleterious	None	None	None	None	N
I/L	0.1183	likely_benign	0.1086	benign	-0.516	Destabilizing	0.015	N	0.303	neutral	N	0.356969773	None	None	N
I/M	0.1929	likely_benign	0.1678	benign	-0.514	Destabilizing	0.976	D	0.626	neutral	N	0.476573025	None	None	N
I/N	0.9653	likely_pathogenic	0.9357	pathogenic	-2.211	Highly Destabilizing	0.996	D	0.787	deleterious	N	0.492728723	None	None	N
I/P	0.9351	likely_pathogenic	0.9219	pathogenic	-1.063	Destabilizing	0.991	D	0.783	deleterious	None	None	None	None	N
I/Q	0.982	likely_pathogenic	0.967	pathogenic	-1.949	Destabilizing	0.997	D	0.787	deleterious	None	None	None	None	N
I/R	0.9777	likely_pathogenic	0.9613	pathogenic	-1.674	Destabilizing	0.991	D	0.784	deleterious	None	None	None	None	N
I/S	0.9527	likely_pathogenic	0.9184	pathogenic	-2.795	Highly Destabilizing	0.852	D	0.715	prob.delet.	N	0.481118929	None	None	N
I/T	0.9248	likely_pathogenic	0.8894	pathogenic	-2.355	Highly Destabilizing	0.92	D	0.704	prob.neutral	N	0.50357805	None	None	N
I/V	0.0776	likely_benign	0.0789	benign	-1.063	Destabilizing	0.134	N	0.269	neutral	N	0.405806657	None	None	N
I/W	0.9824	likely_pathogenic	0.971	pathogenic	-1.75	Destabilizing	0.999	D	0.771	deleterious	None	None	None	None	N
I/Y	0.9337	likely_pathogenic	0.8891	pathogenic	-1.383	Destabilizing	0.997	D	0.708	prob.delet.	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.