TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29030	87313;87314;87315	chr2:178558371;178558370;178558369	chr2:179423098;179423097;179423096
N2AB	27389	82390;82391;82392	chr2:178558371;178558370;178558369	chr2:179423098;179423097;179423096
N2A	26462	79609;79610;79611	chr2:178558371;178558370;178558369	chr2:179423098;179423097;179423096
N2B	19965	60118;60119;60120	chr2:178558371;178558370;178558369	chr2:179423098;179423097;179423096
Novex-1	20090	60493;60494;60495	chr2:178558371;178558370;178558369	chr2:179423098;179423097;179423096
Novex-2	20157	60694;60695;60696	chr2:178558371;178558370;178558369	chr2:179423098;179423097;179423096
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Fn3-99
• Domain position: 89
• Structural Position: 124
• Q(SASA): 0.4721
• 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/P	None	None	0.028	N	0.609	0.204	0.540788926979	gnomAD-4.0.0	1.59212E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85879E-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	0.3177	likely_benign	0.2547	benign	-0.552	Destabilizing	0.841	D	0.595	neutral	None	None	None	None	I
L/C	0.6182	likely_pathogenic	0.5528	ambiguous	-0.84	Destabilizing	0.998	D	0.623	neutral	None	None	None	None	I
L/D	0.7616	likely_pathogenic	0.7006	pathogenic	-0.296	Destabilizing	0.974	D	0.781	deleterious	None	None	None	None	I
L/E	0.5441	ambiguous	0.4741	ambiguous	-0.361	Destabilizing	0.949	D	0.765	deleterious	None	None	None	None	I
L/F	0.1875	likely_benign	0.1582	benign	-0.588	Destabilizing	0.974	D	0.529	neutral	None	None	None	None	I
L/G	0.5665	likely_pathogenic	0.4816	ambiguous	-0.673	Destabilizing	0.949	D	0.737	deleterious	None	None	None	None	I
L/H	0.3339	likely_benign	0.2819	benign	0.127	Stabilizing	0.998	D	0.781	deleterious	None	None	None	None	I
L/I	0.12	likely_benign	0.1	benign	-0.337	Destabilizing	0.066	N	0.295	neutral	None	None	None	None	I
L/K	0.4604	ambiguous	0.3958	ambiguous	-0.392	Destabilizing	0.949	D	0.731	deleterious	None	None	None	None	I
L/M	0.1475	likely_benign	0.1315	benign	-0.717	Destabilizing	0.966	D	0.507	neutral	N	0.470263567	None	None	I
L/N	0.465	ambiguous	0.3767	ambiguous	-0.353	Destabilizing	0.974	D	0.795	deleterious	None	None	None	None	I
L/P	0.2465	likely_benign	0.2026	benign	-0.382	Destabilizing	0.028	N	0.609	neutral	N	0.389898629	None	None	I
L/Q	0.2447	likely_benign	0.2002	benign	-0.495	Destabilizing	0.966	D	0.779	deleterious	N	0.477901616	None	None	I
L/R	0.3397	likely_benign	0.2939	benign	0.073	Stabilizing	0.966	D	0.783	deleterious	N	0.488598612	None	None	I
L/S	0.3824	ambiguous	0.299	benign	-0.738	Destabilizing	0.949	D	0.617	neutral	None	None	None	None	I
L/T	0.3071	likely_benign	0.242	benign	-0.702	Destabilizing	0.841	D	0.633	neutral	None	None	None	None	I
L/V	0.1195	likely_benign	0.0992	benign	-0.382	Destabilizing	0.051	N	0.233	neutral	N	0.38537267	None	None	I
L/W	0.3851	ambiguous	0.3411	ambiguous	-0.604	Destabilizing	0.998	D	0.765	deleterious	None	None	None	None	I
L/Y	0.4445	ambiguous	0.3871	ambiguous	-0.386	Destabilizing	0.991	D	0.567	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.