TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5938	18037;18038;18039	chr2:178730721;178730720;178730719	chr2:179595448;179595447;179595446
N2AB	5621	17086;17087;17088	chr2:178730721;178730720;178730719	chr2:179595448;179595447;179595446
N2A	4694	14305;14306;14307	chr2:178730721;178730720;178730719	chr2:179595448;179595447;179595446
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: TTA
• RefSeq wild type template codon: AAT
• Domain: Ig-43
• Domain position: 20
• Structural Position: 30
• Q(SASA): 0.1603
• 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/F	rs1217786152	None	0.999	N	0.793	0.409	0.500050830518	gnomAD-4.0.0	1.20033E-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
L/A	0.9245	likely_pathogenic	0.907	pathogenic	-2.387	Highly Destabilizing	0.997	D	0.761	deleterious	None	None	None	None	N
L/C	0.9492	likely_pathogenic	0.9382	pathogenic	-1.675	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	N
L/D	0.9991	likely_pathogenic	0.9991	pathogenic	-3.158	Highly Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
L/E	0.9936	likely_pathogenic	0.9929	pathogenic	-2.883	Highly Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
L/F	0.3042	likely_benign	0.2818	benign	-1.563	Destabilizing	0.999	D	0.793	deleterious	N	0.512068196	None	None	N
L/G	0.9902	likely_pathogenic	0.989	pathogenic	-2.915	Highly Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
L/H	0.976	likely_pathogenic	0.9724	pathogenic	-2.516	Highly Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
L/I	0.2434	likely_benign	0.226	benign	-0.815	Destabilizing	0.992	D	0.689	prob.neutral	D	0.551213818	None	None	N
L/K	0.9856	likely_pathogenic	0.9848	pathogenic	-1.869	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
L/M	0.1414	likely_benign	0.1359	benign	-0.85	Destabilizing	0.985	D	0.626	neutral	None	None	None	None	N
L/N	0.9946	likely_pathogenic	0.9943	pathogenic	-2.441	Highly Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
L/P	0.9976	likely_pathogenic	0.9977	pathogenic	-1.328	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
L/Q	0.9633	likely_pathogenic	0.9574	pathogenic	-2.199	Highly Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
L/R	0.9784	likely_pathogenic	0.974	pathogenic	-1.869	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
L/S	0.985	likely_pathogenic	0.9819	pathogenic	-2.987	Highly Destabilizing	0.999	D	0.851	deleterious	D	0.639829276	None	None	N
L/T	0.9435	likely_pathogenic	0.9316	pathogenic	-2.556	Highly Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
L/V	0.293	likely_benign	0.258	benign	-1.328	Destabilizing	0.992	D	0.692	prob.neutral	D	0.579386103	None	None	N
L/W	0.8507	likely_pathogenic	0.8293	pathogenic	-1.931	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
L/Y	0.9006	likely_pathogenic	0.8989	pathogenic	-1.633	Destabilizing	1.0	D	0.793	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.