TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23845	71758;71759;71760	chr2:178574599;178574598;178574597	chr2:179439326;179439325;179439324
N2AB	22204	66835;66836;66837	chr2:178574599;178574598;178574597	chr2:179439326;179439325;179439324
N2A	21277	64054;64055;64056	chr2:178574599;178574598;178574597	chr2:179439326;179439325;179439324
N2B	14780	44563;44564;44565	chr2:178574599;178574598;178574597	chr2:179439326;179439325;179439324
Novex-1	14905	44938;44939;44940	chr2:178574599;178574598;178574597	chr2:179439326;179439325;179439324
Novex-2	14972	45139;45140;45141	chr2:178574599;178574598;178574597	chr2:179439326;179439325;179439324
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: Fn3-61
• Domain position: 20
• Structural Position: 22
• Q(SASA): 0.0973
• 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/V	None	None	0.002	N	0.178	0.073	0.344483371355	gnomAD-4.0.0	1.36872E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79922E-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	0.8929	likely_pathogenic	0.8595	pathogenic	-2.31	Highly Destabilizing	0.25	N	0.719	prob.delet.	None	None	None	None	N
I/C	0.9224	likely_pathogenic	0.8973	pathogenic	-1.55	Destabilizing	0.992	D	0.801	deleterious	None	None	None	None	N
I/D	0.999	likely_pathogenic	0.9985	pathogenic	-2.768	Highly Destabilizing	0.972	D	0.879	deleterious	None	None	None	None	N
I/E	0.9971	likely_pathogenic	0.996	pathogenic	-2.454	Highly Destabilizing	0.92	D	0.86	deleterious	None	None	None	None	N
I/F	0.6002	likely_pathogenic	0.4964	ambiguous	-1.316	Destabilizing	0.81	D	0.737	prob.delet.	N	0.479420181	None	None	N
I/G	0.991	likely_pathogenic	0.9861	pathogenic	-2.927	Highly Destabilizing	0.92	D	0.845	deleterious	None	None	None	None	N
I/H	0.9949	likely_pathogenic	0.9922	pathogenic	-2.672	Highly Destabilizing	0.992	D	0.887	deleterious	None	None	None	None	N
I/K	0.9952	likely_pathogenic	0.9933	pathogenic	-1.609	Destabilizing	0.92	D	0.844	deleterious	None	None	None	None	N
I/L	0.1328	likely_benign	0.12	benign	-0.483	Destabilizing	0.002	N	0.237	neutral	N	0.393002357	None	None	N
I/M	0.2961	likely_benign	0.2447	benign	-0.657	Destabilizing	0.81	D	0.665	neutral	N	0.481573001	None	None	N
I/N	0.9865	likely_pathogenic	0.9815	pathogenic	-2.226	Highly Destabilizing	0.963	D	0.885	deleterious	N	0.5206948	None	None	N
I/P	0.9965	likely_pathogenic	0.9942	pathogenic	-1.078	Destabilizing	0.972	D	0.881	deleterious	None	None	None	None	N
I/Q	0.9942	likely_pathogenic	0.9915	pathogenic	-1.886	Destabilizing	0.972	D	0.885	deleterious	None	None	None	None	N
I/R	0.9919	likely_pathogenic	0.9885	pathogenic	-1.721	Destabilizing	0.92	D	0.884	deleterious	None	None	None	None	N
I/S	0.9751	likely_pathogenic	0.9641	pathogenic	-2.861	Highly Destabilizing	0.81	D	0.815	deleterious	N	0.52044131	None	None	N
I/T	0.9412	likely_pathogenic	0.9235	pathogenic	-2.377	Highly Destabilizing	0.549	D	0.718	prob.delet.	N	0.52044131	None	None	N
I/V	0.0777	likely_benign	0.0731	benign	-1.078	Destabilizing	0.002	N	0.178	neutral	N	0.422946836	None	None	N
I/W	0.9953	likely_pathogenic	0.9916	pathogenic	-1.752	Destabilizing	0.992	D	0.872	deleterious	None	None	None	None	N
I/Y	0.9694	likely_pathogenic	0.9545	pathogenic	-1.429	Destabilizing	0.92	D	0.793	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.