TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20627	62104;62105;62106	chr2:178589846;178589845;178589844	chr2:179454573;179454572;179454571
N2AB	18986	57181;57182;57183	chr2:178589846;178589845;178589844	chr2:179454573;179454572;179454571
N2A	18059	54400;54401;54402	chr2:178589846;178589845;178589844	chr2:179454573;179454572;179454571
N2B	11562	34909;34910;34911	chr2:178589846;178589845;178589844	chr2:179454573;179454572;179454571
Novex-1	11687	35284;35285;35286	chr2:178589846;178589845;178589844	chr2:179454573;179454572;179454571
Novex-2	11754	35485;35486;35487	chr2:178589846;178589845;178589844	chr2:179454573;179454572;179454571
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: Fn3-37
• Domain position: 59
• Structural Position: 91
• Q(SASA): 0.2242
• 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/S	None	None	0.001	N	0.479	0.32	0.527809512145	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	0.3053	likely_benign	0.2768	benign	-1.296	Destabilizing	0.116	N	0.447	neutral	None	None	None	None	N
L/C	0.483	ambiguous	0.427	ambiguous	-0.88	Destabilizing	0.944	D	0.494	neutral	None	None	None	None	N
L/D	0.8198	likely_pathogenic	0.7773	pathogenic	-0.552	Destabilizing	0.69	D	0.592	neutral	None	None	None	None	N
L/E	0.5142	ambiguous	0.4636	ambiguous	-0.51	Destabilizing	0.241	N	0.56	neutral	None	None	None	None	N
L/F	0.1614	likely_benign	0.1569	benign	-0.674	Destabilizing	0.627	D	0.46	neutral	N	0.415719793	None	None	N
L/G	0.6514	likely_pathogenic	0.6218	pathogenic	-1.631	Destabilizing	0.241	N	0.557	neutral	None	None	None	None	N
L/H	0.3058	likely_benign	0.2794	benign	-0.673	Destabilizing	0.944	D	0.6	neutral	None	None	None	None	N
L/I	0.092	likely_benign	0.0936	benign	-0.447	Destabilizing	0.193	N	0.426	neutral	N	0.46686069	None	None	N
L/K	0.4024	ambiguous	0.3487	ambiguous	-0.877	Destabilizing	0.004	N	0.407	neutral	None	None	None	None	N
L/M	0.0981	likely_benign	0.0973	benign	-0.499	Destabilizing	0.008	N	0.349	neutral	None	None	None	None	N
L/N	0.4038	ambiguous	0.3633	ambiguous	-0.868	Destabilizing	0.527	D	0.591	neutral	None	None	None	None	N
L/P	0.8514	likely_pathogenic	0.8569	pathogenic	-0.698	Destabilizing	0.69	D	0.593	neutral	None	None	None	None	N
L/Q	0.2057	likely_benign	0.188	benign	-0.941	Destabilizing	0.69	D	0.571	neutral	None	None	None	None	N
L/R	0.3961	ambiguous	0.351	ambiguous	-0.368	Destabilizing	0.241	N	0.555	neutral	None	None	None	None	N
L/S	0.358	ambiguous	0.3243	benign	-1.507	Destabilizing	0.001	N	0.479	neutral	N	0.474365452	None	None	N
L/T	0.2295	likely_benign	0.2087	benign	-1.339	Destabilizing	0.241	N	0.433	neutral	None	None	None	None	N
L/V	0.091	likely_benign	0.0925	benign	-0.698	Destabilizing	0.09	N	0.462	neutral	N	0.463046807	None	None	N
L/W	0.3716	ambiguous	0.31	benign	-0.77	Destabilizing	0.981	D	0.611	neutral	None	None	None	None	N
L/Y	0.3777	ambiguous	0.3317	benign	-0.525	Destabilizing	0.818	D	0.51	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.