TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19716	59371;59372;59373	chr2:178592973;178592972;178592971	chr2:179457700;179457699;179457698
N2AB	18075	54448;54449;54450	chr2:178592973;178592972;178592971	chr2:179457700;179457699;179457698
N2A	17148	51667;51668;51669	chr2:178592973;178592972;178592971	chr2:179457700;179457699;179457698
N2B	10651	32176;32177;32178	chr2:178592973;178592972;178592971	chr2:179457700;179457699;179457698
Novex-1	10776	32551;32552;32553	chr2:178592973;178592972;178592971	chr2:179457700;179457699;179457698
Novex-2	10843	32752;32753;32754	chr2:178592973;178592972;178592971	chr2:179457700;179457699;179457698
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: Fn3-31
• Domain position: 37
• Structural Position: 39
• Q(SASA): 0.1125
• 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/T	rs763636451	-2.685	0.891	N	0.727	0.285	0.744399525587	gnomAD-4.0.0	2.05289E-06	None	None	None	None	N	None	0	2.23684E-05	None	0	0	None	0	0	1.79914E-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	0.4037	ambiguous	0.4318	ambiguous	-2.937	Highly Destabilizing	0.688	D	0.713	prob.delet.	None	None	None	None	N
I/C	0.6643	likely_pathogenic	0.7097	pathogenic	-2.391	Highly Destabilizing	0.998	D	0.685	prob.neutral	None	None	None	None	N
I/D	0.8672	likely_pathogenic	0.8802	pathogenic	-3.531	Highly Destabilizing	0.974	D	0.739	prob.delet.	None	None	None	None	N
I/E	0.7308	likely_pathogenic	0.7458	pathogenic	-3.346	Highly Destabilizing	0.842	D	0.733	prob.delet.	None	None	None	None	N
I/F	0.1566	likely_benign	0.1676	benign	-1.661	Destabilizing	0.934	D	0.747	deleterious	N	0.461068081	None	None	N
I/G	0.8191	likely_pathogenic	0.8383	pathogenic	-3.397	Highly Destabilizing	0.974	D	0.735	prob.delet.	None	None	None	None	N
I/H	0.4981	ambiguous	0.5188	ambiguous	-2.61	Highly Destabilizing	0.998	D	0.721	prob.delet.	None	None	None	None	N
I/K	0.4865	ambiguous	0.5103	ambiguous	-2.271	Highly Destabilizing	0.067	N	0.665	neutral	None	None	None	None	N
I/L	0.0921	likely_benign	0.1001	benign	-1.599	Destabilizing	0.002	N	0.249	neutral	N	0.421144256	None	None	N
I/M	0.1043	likely_benign	0.1059	benign	-1.74	Destabilizing	0.934	D	0.738	prob.delet.	N	0.469064607	None	None	N
I/N	0.4723	ambiguous	0.4891	ambiguous	-2.585	Highly Destabilizing	0.966	D	0.742	deleterious	N	0.508069807	None	None	N
I/P	0.9813	likely_pathogenic	0.9805	pathogenic	-2.03	Highly Destabilizing	0.991	D	0.741	deleterious	None	None	None	None	N
I/Q	0.5592	ambiguous	0.5834	pathogenic	-2.526	Highly Destabilizing	0.949	D	0.742	deleterious	None	None	None	None	N
I/R	0.3859	ambiguous	0.3989	ambiguous	-1.823	Destabilizing	0.904	D	0.741	deleterious	None	None	None	None	N
I/S	0.4262	ambiguous	0.4452	ambiguous	-3.179	Highly Destabilizing	0.801	D	0.706	prob.neutral	N	0.479459054	None	None	N
I/T	0.2052	likely_benign	0.2202	benign	-2.876	Highly Destabilizing	0.891	D	0.727	prob.delet.	N	0.466857903	None	None	N
I/V	0.0789	likely_benign	0.0861	benign	-2.03	Highly Destabilizing	0.267	N	0.429	neutral	N	0.423915202	None	None	N
I/W	0.6835	likely_pathogenic	0.704	pathogenic	-1.975	Destabilizing	0.998	D	0.723	prob.delet.	None	None	None	None	N
I/Y	0.4813	ambiguous	0.5033	ambiguous	-1.84	Destabilizing	0.974	D	0.719	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.