TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7073	21442;21443;21444	chr2:178724042;178724041;178724040	chr2:179588769;179588768;179588767
N2AB	6756	20491;20492;20493	chr2:178724042;178724041;178724040	chr2:179588769;179588768;179588767
N2A	5829	17710;17711;17712	chr2:178724042;178724041;178724040	chr2:179588769;179588768;179588767
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: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-55
• Domain position: 30
• Structural Position: 44
• Q(SASA): 0.1445
• 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/M	None	None	0.136	N	0.233	0.068	0.296679040009	gnomAD-4.0.0	1.59199E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8595E-06	0	0
I/V	rs1321725183	-1.549	0.267	N	0.383	0.139	0.415055319159	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.58E-05	None	0	None	0	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	0.81	likely_pathogenic	0.804	pathogenic	-2.127	Highly Destabilizing	0.688	D	0.555	neutral	None	None	None	None	N
I/C	0.9365	likely_pathogenic	0.9456	pathogenic	-1.512	Destabilizing	0.998	D	0.644	neutral	None	None	None	None	N
I/D	0.9828	likely_pathogenic	0.9885	pathogenic	-1.404	Destabilizing	0.991	D	0.721	prob.delet.	None	None	None	None	N
I/E	0.971	likely_pathogenic	0.9795	pathogenic	-1.32	Destabilizing	0.974	D	0.716	prob.delet.	None	None	None	None	N
I/F	0.3261	likely_benign	0.3571	ambiguous	-1.459	Destabilizing	0.801	D	0.617	neutral	D	0.532558112	None	None	N
I/G	0.963	likely_pathogenic	0.9678	pathogenic	-2.544	Highly Destabilizing	0.974	D	0.721	prob.delet.	None	None	None	None	N
I/H	0.9441	likely_pathogenic	0.9542	pathogenic	-1.783	Destabilizing	0.998	D	0.666	neutral	None	None	None	None	N
I/K	0.9271	likely_pathogenic	0.9434	pathogenic	-1.383	Destabilizing	0.949	D	0.719	prob.delet.	None	None	None	None	N
I/L	0.1668	likely_benign	0.16	benign	-1.003	Destabilizing	0.002	N	0.119	neutral	N	0.471160149	None	None	N
I/M	0.2398	likely_benign	0.2232	benign	-0.892	Destabilizing	0.136	N	0.233	neutral	N	0.486124083	None	None	N
I/N	0.864	likely_pathogenic	0.8997	pathogenic	-1.309	Destabilizing	0.989	D	0.731	prob.delet.	N	0.518560385	None	None	N
I/P	0.855	likely_pathogenic	0.8883	pathogenic	-1.35	Destabilizing	0.991	D	0.729	prob.delet.	None	None	None	None	N
I/Q	0.9295	likely_pathogenic	0.944	pathogenic	-1.385	Destabilizing	0.974	D	0.732	prob.delet.	None	None	None	None	N
I/R	0.8772	likely_pathogenic	0.9054	pathogenic	-0.926	Destabilizing	0.974	D	0.713	prob.delet.	None	None	None	None	N
I/S	0.8551	likely_pathogenic	0.8749	pathogenic	-2.083	Highly Destabilizing	0.891	D	0.661	neutral	N	0.482832401	None	None	N
I/T	0.8727	likely_pathogenic	0.8801	pathogenic	-1.863	Destabilizing	0.801	D	0.601	neutral	N	0.499949151	None	None	N
I/V	0.1163	likely_benign	0.1035	benign	-1.35	Destabilizing	0.267	N	0.383	neutral	N	0.484945541	None	None	N
I/W	0.9547	likely_pathogenic	0.959	pathogenic	-1.568	Destabilizing	0.998	D	0.662	neutral	None	None	None	None	N
I/Y	0.8235	likely_pathogenic	0.8504	pathogenic	-1.33	Destabilizing	0.974	D	0.689	prob.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.