TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7057	21394;21395;21396	chr2:178724090;178724089;178724088	chr2:179588817;179588816;179588815
N2AB	6740	20443;20444;20445	chr2:178724090;178724089;178724088	chr2:179588817;179588816;179588815
N2A	5813	17662;17663;17664	chr2:178724090;178724089;178724088	chr2:179588817;179588816;179588815
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-55
• Domain position: 14
• Structural Position: 23
• Q(SASA): 0.6571
• Predicted PPI site: I

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	0.994	N	0.341	0.19	0.336892272479	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	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	0.1148	likely_benign	0.1112	benign	-0.717	Destabilizing	0.931	D	0.437	neutral	None	None	None	None	I
L/C	0.4106	ambiguous	0.4013	ambiguous	-0.738	Destabilizing	1.0	D	0.447	neutral	None	None	None	None	I
L/D	0.4644	ambiguous	0.4479	ambiguous	0.002	Stabilizing	0.996	D	0.567	neutral	None	None	None	None	I
L/E	0.2062	likely_benign	0.2073	benign	-0.066	Destabilizing	0.97	D	0.502	neutral	None	None	None	None	I
L/F	0.101	likely_benign	0.0936	benign	-0.56	Destabilizing	0.994	D	0.341	neutral	N	0.461794954	None	None	I
L/G	0.3091	likely_benign	0.2933	benign	-0.91	Destabilizing	0.996	D	0.503	neutral	None	None	None	None	I
L/H	0.1517	likely_benign	0.1387	benign	-0.119	Destabilizing	1.0	D	0.563	neutral	None	None	None	None	I
L/I	0.0792	likely_benign	0.0848	benign	-0.322	Destabilizing	0.925	D	0.44	neutral	N	0.480989488	None	None	I
L/K	0.1471	likely_benign	0.1564	benign	-0.421	Destabilizing	0.155	N	0.23	neutral	None	None	None	None	I
L/M	0.1102	likely_benign	0.1131	benign	-0.423	Destabilizing	0.996	D	0.364	neutral	None	None	None	None	I
L/N	0.2688	likely_benign	0.2611	benign	-0.284	Destabilizing	0.996	D	0.569	neutral	None	None	None	None	I
L/P	0.1528	likely_benign	0.1514	benign	-0.42	Destabilizing	0.999	D	0.574	neutral	None	None	None	None	I
L/Q	0.0962	likely_benign	0.094	benign	-0.466	Destabilizing	0.991	D	0.526	neutral	None	None	None	None	I
L/R	0.1054	likely_benign	0.1006	benign	0.106	Stabilizing	0.983	D	0.455	neutral	None	None	None	None	I
L/S	0.1279	likely_benign	0.116	benign	-0.807	Destabilizing	0.961	D	0.477	neutral	N	0.474063516	None	None	I
L/T	0.1224	likely_benign	0.1217	benign	-0.761	Destabilizing	0.97	D	0.454	neutral	None	None	None	None	I
L/V	0.0841	likely_benign	0.0839	benign	-0.42	Destabilizing	0.248	N	0.18	neutral	N	0.417668728	None	None	I
L/W	0.1646	likely_benign	0.1432	benign	-0.575	Destabilizing	1.0	D	0.648	neutral	None	None	None	None	I
L/Y	0.2483	likely_benign	0.2327	benign	-0.335	Destabilizing	0.999	D	0.389	neutral	None	None	None	None	I

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.