TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28921	86986;86987;86988	chr2:178559371;178559370;178559369	chr2:179424098;179424097;179424096
N2AB	27280	82063;82064;82065	chr2:178559371;178559370;178559369	chr2:179424098;179424097;179424096
N2A	26353	79282;79283;79284	chr2:178559371;178559370;178559369	chr2:179424098;179424097;179424096
N2B	19856	59791;59792;59793	chr2:178559371;178559370;178559369	chr2:179424098;179424097;179424096
Novex-1	19981	60166;60167;60168	chr2:178559371;178559370;178559369	chr2:179424098;179424097;179424096
Novex-2	20048	60367;60368;60369	chr2:178559371;178559370;178559369	chr2:179424098;179424097;179424096
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Fn3-98
• Domain position: 77
• Structural Position: 110
• Q(SASA): 0.1414
• 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
G/A	None	None	0.45	N	0.542	0.174	0.110078149338	gnomAD-4.0.0	1.20034E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31252E-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
G/A	0.0887	likely_benign	0.089	benign	-1.223	Destabilizing	0.45	N	0.542	neutral	N	0.30617002	None	None	N
G/C	0.4413	ambiguous	0.4858	ambiguous	-1.733	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
G/D	0.9895	likely_pathogenic	0.9905	pathogenic	-2.828	Highly Destabilizing	0.999	D	0.853	deleterious	None	None	None	None	N
G/E	0.9862	likely_pathogenic	0.9879	pathogenic	-2.65	Highly Destabilizing	0.997	D	0.825	deleterious	N	0.467659028	None	None	N
G/F	0.9882	likely_pathogenic	0.9903	pathogenic	-0.466	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
G/H	0.993	likely_pathogenic	0.9932	pathogenic	-1.554	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
G/I	0.8827	likely_pathogenic	0.9116	pathogenic	-0.341	Destabilizing	0.999	D	0.874	deleterious	None	None	None	None	N
G/K	0.9962	likely_pathogenic	0.9965	pathogenic	-1.219	Destabilizing	0.998	D	0.823	deleterious	None	None	None	None	N
G/L	0.9046	likely_pathogenic	0.9154	pathogenic	-0.341	Destabilizing	0.996	D	0.846	deleterious	None	None	None	None	N
G/M	0.9453	likely_pathogenic	0.9517	pathogenic	-0.942	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
G/N	0.9788	likely_pathogenic	0.9815	pathogenic	-1.693	Destabilizing	0.999	D	0.815	deleterious	None	None	None	None	N
G/P	0.8705	likely_pathogenic	0.8993	pathogenic	-0.605	Destabilizing	0.999	D	0.849	deleterious	None	None	None	None	N
G/Q	0.9844	likely_pathogenic	0.985	pathogenic	-1.482	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
G/R	0.9832	likely_pathogenic	0.9845	pathogenic	-1.312	Destabilizing	0.999	D	0.859	deleterious	N	0.467912518	None	None	N
G/S	0.2792	likely_benign	0.2764	benign	-1.888	Destabilizing	0.996	D	0.791	deleterious	None	None	None	None	N
G/T	0.6655	likely_pathogenic	0.6888	pathogenic	-1.625	Destabilizing	0.998	D	0.826	deleterious	None	None	None	None	N
G/V	0.6809	likely_pathogenic	0.7362	pathogenic	-0.605	Destabilizing	0.995	D	0.848	deleterious	N	0.489830763	None	None	N
G/W	0.9877	likely_pathogenic	0.9891	pathogenic	-1.108	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
G/Y	0.9886	likely_pathogenic	0.9906	pathogenic	-0.774	Destabilizing	1.0	D	0.869	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.