TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15037	45334;45335;45336	chr2:178621715;178621714;178621713	chr2:179486442;179486441;179486440
N2AB	13396	40411;40412;40413	chr2:178621715;178621714;178621713	chr2:179486442;179486441;179486440
N2A	12469	37630;37631;37632	chr2:178621715;178621714;178621713	chr2:179486442;179486441;179486440
N2B	5972	18139;18140;18141	chr2:178621715;178621714;178621713	chr2:179486442;179486441;179486440
Novex-1	6097	18514;18515;18516	chr2:178621715;178621714;178621713	chr2:179486442;179486441;179486440
Novex-2	6164	18715;18716;18717	chr2:178621715;178621714;178621713	chr2:179486442;179486441;179486440
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-102
• Domain position: 7
• Structural Position: 8
• Q(SASA): 0.2158
• 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
L/P	None	None	1.0	D	0.903	0.681	0.875806401338	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
L/A	0.8524	likely_pathogenic	0.8833	pathogenic	-2.198	Highly Destabilizing	0.999	D	0.674	neutral	None	None	None	None	N
L/C	0.9457	likely_pathogenic	0.9552	pathogenic	-1.448	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
L/D	0.9969	likely_pathogenic	0.997	pathogenic	-1.898	Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
L/E	0.9836	likely_pathogenic	0.9841	pathogenic	-1.844	Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
L/F	0.7109	likely_pathogenic	0.7036	pathogenic	-1.585	Destabilizing	1.0	D	0.727	prob.delet.	D	0.704320392	None	None	N
L/G	0.978	likely_pathogenic	0.9832	pathogenic	-2.595	Highly Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
L/H	0.9695	likely_pathogenic	0.9674	pathogenic	-1.82	Destabilizing	1.0	D	0.875	deleterious	D	0.79670018	None	None	N
L/I	0.2213	likely_benign	0.2208	benign	-1.129	Destabilizing	0.999	D	0.479	neutral	D	0.659255324	None	None	N
L/K	0.9735	likely_pathogenic	0.9735	pathogenic	-1.487	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
L/M	0.3258	likely_benign	0.3177	benign	-0.855	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
L/N	0.9813	likely_pathogenic	0.9836	pathogenic	-1.388	Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
L/P	0.8818	likely_pathogenic	0.8942	pathogenic	-1.458	Destabilizing	1.0	D	0.903	deleterious	D	0.547201558	None	None	N
L/Q	0.9432	likely_pathogenic	0.9442	pathogenic	-1.536	Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
L/R	0.9533	likely_pathogenic	0.9531	pathogenic	-0.915	Destabilizing	1.0	D	0.89	deleterious	D	0.725693872	None	None	N
L/S	0.9709	likely_pathogenic	0.9731	pathogenic	-2.077	Highly Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
L/T	0.8472	likely_pathogenic	0.8605	pathogenic	-1.898	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
L/V	0.2932	likely_benign	0.293	benign	-1.458	Destabilizing	0.999	D	0.459	neutral	D	0.705044022	None	None	N
L/W	0.9656	likely_pathogenic	0.955	pathogenic	-1.719	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
L/Y	0.9784	likely_pathogenic	0.9754	pathogenic	-1.498	Destabilizing	1.0	D	0.868	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.