TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9624	29095;29096;29097	chr2:178707697;178707696;178707695	chr2:179572424;179572423;179572422
N2AB	9307	28144;28145;28146	chr2:178707697;178707696;178707695	chr2:179572424;179572423;179572422
N2A	8380	25363;25364;25365	chr2:178707697;178707696;178707695	chr2:179572424;179572423;179572422
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: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Ig-82
• Domain position: 35
• Structural Position: 49
• Q(SASA): 0.2359
• 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/W	None	None	1.0	None	0.732	0.437	0.747836230633	gnomAD-4.0.0	1.59101E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43283E-05	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	0.6479	likely_pathogenic	0.5283	ambiguous	-2.183	Highly Destabilizing	0.871	D	0.579	neutral	None	None	None	None	N
L/C	0.7944	likely_pathogenic	0.6971	pathogenic	-1.526	Destabilizing	1.0	D	0.675	neutral	None	None	None	None	N
L/D	0.9469	likely_pathogenic	0.893	pathogenic	-2.034	Highly Destabilizing	0.991	D	0.748	deleterious	None	None	None	None	N
L/E	0.6389	likely_pathogenic	0.4835	ambiguous	-1.879	Destabilizing	0.991	D	0.72	prob.delet.	None	None	None	None	N
L/F	0.1811	likely_benign	0.1564	benign	-1.276	Destabilizing	0.989	D	0.571	neutral	None	None	None	None	N
L/G	0.8482	likely_pathogenic	0.7545	pathogenic	-2.662	Highly Destabilizing	0.97	D	0.713	prob.delet.	None	None	None	None	N
L/H	0.4452	ambiguous	0.3178	benign	-2.006	Highly Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
L/I	0.1459	likely_benign	0.1374	benign	-0.847	Destabilizing	0.942	D	0.52	neutral	None	None	None	None	N
L/K	0.5439	ambiguous	0.4013	ambiguous	-1.599	Destabilizing	0.991	D	0.694	prob.neutral	None	None	None	None	N
L/M	0.1176	likely_benign	0.1082	benign	-0.819	Destabilizing	0.489	N	0.411	neutral	None	None	None	None	N
L/N	0.6954	likely_pathogenic	0.5887	pathogenic	-1.73	Destabilizing	0.991	D	0.745	deleterious	None	None	None	None	N
L/P	0.9904	likely_pathogenic	0.9835	pathogenic	-1.268	Destabilizing	0.999	D	0.757	deleterious	None	None	None	None	N
L/Q	0.2258	likely_benign	0.1457	benign	-1.698	Destabilizing	0.996	D	0.724	prob.delet.	None	None	None	None	N
L/R	0.4572	ambiguous	0.2919	benign	-1.222	Destabilizing	0.996	D	0.727	prob.delet.	None	None	None	None	N
L/S	0.6125	likely_pathogenic	0.4773	ambiguous	-2.451	Highly Destabilizing	0.489	N	0.549	neutral	None	None	None	None	N
L/T	0.5125	ambiguous	0.4007	ambiguous	-2.162	Highly Destabilizing	0.97	D	0.576	neutral	None	None	None	None	N
L/V	0.1491	likely_benign	0.1376	benign	-1.268	Destabilizing	0.835	D	0.572	neutral	None	None	None	None	N
L/W	0.36	ambiguous	0.2609	benign	-1.56	Destabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	N
L/Y	0.4718	ambiguous	0.4043	ambiguous	-1.275	Destabilizing	0.999	D	0.691	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.