TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6067	18424;18425;18426	chr2:178730201;178730200;178730199	chr2:179594928;179594927;179594926
N2AB	5750	17473;17474;17475	chr2:178730201;178730200;178730199	chr2:179594928;179594927;179594926
N2A	4823	14692;14693;14694	chr2:178730201;178730200;178730199	chr2:179594928;179594927;179594926
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: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-44
• Domain position: 56
• Structural Position: 136
• Q(SASA): 0.1447
• 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
T/I	None	None	0.896	N	0.812	0.112	0.236890367714	gnomAD-4.0.0	1.59199E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85905E-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
T/A	0.0693	likely_benign	0.0695	benign	-1.344	Destabilizing	0.007	N	0.449	neutral	N	0.428232439	None	None	N
T/C	0.2827	likely_benign	0.2932	benign	-0.616	Destabilizing	0.992	D	0.772	deleterious	None	None	None	None	N
T/D	0.7497	likely_pathogenic	0.8216	pathogenic	-1.675	Destabilizing	0.617	D	0.792	deleterious	None	None	None	None	N
T/E	0.7355	likely_pathogenic	0.8151	pathogenic	-1.389	Destabilizing	0.617	D	0.795	deleterious	None	None	None	None	N
T/F	0.2849	likely_benign	0.3791	ambiguous	-0.904	Destabilizing	0.92	D	0.813	deleterious	None	None	None	None	N
T/G	0.2695	likely_benign	0.274	benign	-1.791	Destabilizing	0.25	N	0.743	deleterious	None	None	None	None	N
T/H	0.4609	ambiguous	0.5202	ambiguous	-1.631	Destabilizing	0.977	D	0.78	deleterious	None	None	None	None	N
T/I	0.2209	likely_benign	0.2992	benign	-0.119	Destabilizing	0.896	D	0.812	deleterious	N	0.462307727	None	None	N
T/K	0.7119	likely_pathogenic	0.7941	pathogenic	0.031	Stabilizing	0.447	N	0.792	deleterious	None	None	None	None	N
T/L	0.1531	likely_benign	0.1901	benign	-0.119	Destabilizing	0.617	D	0.78	deleterious	None	None	None	None	N
T/M	0.1343	likely_benign	0.1622	benign	-0.296	Destabilizing	0.972	D	0.783	deleterious	None	None	None	None	N
T/N	0.2906	likely_benign	0.3485	ambiguous	-0.917	Destabilizing	0.379	N	0.739	prob.delet.	N	0.448359782	None	None	N
T/P	0.5812	likely_pathogenic	0.6217	pathogenic	-0.502	Destabilizing	0.896	D	0.813	deleterious	N	0.45842206	None	None	N
T/Q	0.5595	ambiguous	0.6385	pathogenic	-0.524	Destabilizing	0.85	D	0.816	deleterious	None	None	None	None	N
T/R	0.5886	likely_pathogenic	0.6798	pathogenic	-0.442	Destabilizing	0.85	D	0.819	deleterious	None	None	None	None	N
T/S	0.1108	likely_benign	0.1098	benign	-1.18	Destabilizing	0.007	N	0.401	neutral	N	0.361180727	None	None	N
T/V	0.149	likely_benign	0.1845	benign	-0.502	Destabilizing	0.617	D	0.712	prob.delet.	None	None	None	None	N
T/W	0.72	likely_pathogenic	0.7875	pathogenic	-1.077	Destabilizing	0.992	D	0.785	deleterious	None	None	None	None	N
T/Y	0.3344	likely_benign	0.4239	ambiguous	-0.679	Destabilizing	0.972	D	0.791	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.