TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2362	7309;7310;7311	chr2:178774084;178774083;178774082	chr2:179638811;179638810;179638809
N2AB	2362	7309;7310;7311	chr2:178774084;178774083;178774082	chr2:179638811;179638810;179638809
N2A	2362	7309;7310;7311	chr2:178774084;178774083;178774082	chr2:179638811;179638810;179638809
N2B	2316	7171;7172;7173	chr2:178774084;178774083;178774082	chr2:179638811;179638810;179638809
Novex-1	2316	7171;7172;7173	chr2:178774084;178774083;178774082	chr2:179638811;179638810;179638809
Novex-2	2316	7171;7172;7173	chr2:178774084;178774083;178774082	chr2:179638811;179638810;179638809
Novex-3	2362	7309;7310;7311	chr2:178774084;178774083;178774082	chr2:179638811;179638810;179638809

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-13
• Domain position: 7
• Structural Position: 8
• Q(SASA): 0.2034
• 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	None	None	1.0	D	0.717	0.637	0.831451841441	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	0.9363	likely_pathogenic	0.9295	pathogenic	-1.698	Destabilizing	0.999	D	0.723	prob.delet.	None	None	None	None	N
L/C	0.9479	likely_pathogenic	0.9369	pathogenic	-1.468	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
L/D	0.9986	likely_pathogenic	0.9983	pathogenic	-0.604	Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	N
L/E	0.9933	likely_pathogenic	0.992	pathogenic	-0.567	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
L/F	0.8119	likely_pathogenic	0.7687	pathogenic	-1.243	Destabilizing	1.0	D	0.717	prob.delet.	D	0.670447136	None	None	N
L/G	0.9896	likely_pathogenic	0.9876	pathogenic	-2.037	Highly Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
L/H	0.9868	likely_pathogenic	0.984	pathogenic	-1.228	Destabilizing	1.0	D	0.851	deleterious	D	0.727875347	None	None	N
L/I	0.25	likely_benign	0.2371	benign	-0.83	Destabilizing	0.999	D	0.522	neutral	D	0.591651532	None	None	N
L/K	0.9894	likely_pathogenic	0.9882	pathogenic	-0.96	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
L/M	0.3983	ambiguous	0.3714	ambiguous	-0.878	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
L/N	0.9867	likely_pathogenic	0.9844	pathogenic	-0.85	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
L/P	0.9307	likely_pathogenic	0.947	pathogenic	-1.089	Destabilizing	1.0	D	0.869	deleterious	D	0.548975028	None	None	N
L/Q	0.9756	likely_pathogenic	0.9711	pathogenic	-0.972	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
L/R	0.9826	likely_pathogenic	0.9795	pathogenic	-0.523	Destabilizing	1.0	D	0.869	deleterious	D	0.728802856	None	None	N
L/S	0.9876	likely_pathogenic	0.9852	pathogenic	-1.637	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
L/T	0.9412	likely_pathogenic	0.9317	pathogenic	-1.467	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
L/V	0.3618	ambiguous	0.3385	benign	-1.089	Destabilizing	0.999	D	0.503	neutral	D	0.671146127	None	None	N
L/W	0.982	likely_pathogenic	0.9751	pathogenic	-1.239	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
L/Y	0.9884	likely_pathogenic	0.9848	pathogenic	-0.99	Destabilizing	1.0	D	0.855	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.