TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13892	41899;41900;41901	chr2:178635650;178635649;178635648	chr2:179500377;179500376;179500375
N2AB	12251	36976;36977;36978	chr2:178635650;178635649;178635648	chr2:179500377;179500376;179500375
N2A	11324	34195;34196;34197	chr2:178635650;178635649;178635648	chr2:179500377;179500376;179500375
N2B	4827	14704;14705;14706	chr2:178635650;178635649;178635648	chr2:179500377;179500376;179500375
Novex-1	4952	15079;15080;15081	chr2:178635650;178635649;178635648	chr2:179500377;179500376;179500375
Novex-2	5019	15280;15281;15282	chr2:178635650;178635649;178635648	chr2:179500377;179500376;179500375
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-89
• Domain position: 17
• Structural Position: 29
• Q(SASA): 0.6102
• 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	0.087	N	0.373	0.012	0.350088858571	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	None	0	0	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	0.4727	ambiguous	0.5877	pathogenic	-1.627	Destabilizing	0.003	N	0.235	neutral	None	None	None	None	N
I/C	0.8333	likely_pathogenic	0.8854	pathogenic	-0.904	Destabilizing	0.204	N	0.395	neutral	None	None	None	None	N
I/D	0.8251	likely_pathogenic	0.8926	pathogenic	-0.899	Destabilizing	0.035	N	0.482	neutral	None	None	None	None	N
I/E	0.7024	likely_pathogenic	0.7832	pathogenic	-0.842	Destabilizing	0.035	N	0.445	neutral	None	None	None	None	N
I/F	0.2746	likely_benign	0.3279	benign	-0.958	Destabilizing	0.026	N	0.348	neutral	N	0.454089933	None	None	N
I/G	0.8321	likely_pathogenic	0.8998	pathogenic	-1.998	Destabilizing	0.035	N	0.461	neutral	None	None	None	None	N
I/H	0.6897	likely_pathogenic	0.774	pathogenic	-1.082	Destabilizing	0.747	D	0.405	neutral	None	None	None	None	N
I/K	0.6545	likely_pathogenic	0.7344	pathogenic	-1.068	Destabilizing	0.035	N	0.443	neutral	None	None	None	None	N
I/L	0.1597	likely_benign	0.1801	benign	-0.661	Destabilizing	None	N	0.169	neutral	N	0.448777195	None	None	N
I/M	0.1743	likely_benign	0.2085	benign	-0.541	Destabilizing	0.087	N	0.373	neutral	N	0.455164241	None	None	N
I/N	0.4041	ambiguous	0.5336	ambiguous	-0.979	Destabilizing	0.026	N	0.499	neutral	N	0.454089933	None	None	N
I/P	0.9681	likely_pathogenic	0.9789	pathogenic	-0.953	Destabilizing	0.068	N	0.52	neutral	None	None	None	None	N
I/Q	0.6474	likely_pathogenic	0.7429	pathogenic	-1.061	Destabilizing	0.204	N	0.489	neutral	None	None	None	None	N
I/R	0.5777	likely_pathogenic	0.6582	pathogenic	-0.551	Destabilizing	0.204	N	0.535	neutral	None	None	None	None	N
I/S	0.393	ambiguous	0.5196	ambiguous	-1.651	Destabilizing	0.006	N	0.344	neutral	N	0.450707854	None	None	N
I/T	0.2154	likely_benign	0.2942	benign	-1.466	Destabilizing	None	N	0.201	neutral	N	0.362126454	None	None	N
I/V	0.0585	likely_benign	0.0639	benign	-0.953	Destabilizing	None	N	0.137	neutral	N	0.395927186	None	None	N
I/W	0.9003	likely_pathogenic	0.921	pathogenic	-1.066	Destabilizing	0.747	D	0.418	neutral	None	None	None	None	N
I/Y	0.6341	likely_pathogenic	0.7035	pathogenic	-0.829	Destabilizing	0.204	N	0.499	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.