TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4716	14371;14372;14373	chr2:178738307;178738306;178738305	chr2:179603034;179603033;179603032
N2AB	4399	13420;13421;13422	chr2:178738307;178738306;178738305	chr2:179603034;179603033;179603032
N2A	3472	10639;10640;10641	chr2:178738307;178738306;178738305	chr2:179603034;179603033;179603032
N2B	4353	13282;13283;13284	chr2:178738307;178738306;178738305	chr2:179603034;179603033;179603032
Novex-1	4478	13657;13658;13659	chr2:178738307;178738306;178738305	chr2:179603034;179603033;179603032
Novex-2	4545	13858;13859;13860	chr2:178738307;178738306;178738305	chr2:179603034;179603033;179603032
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Ig-30
• Domain position: 17
• Structural Position: 26
• Q(SASA): 0.3537
• 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/V	None	None	0.002	N	0.121	0.175	0.180583059064	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	0.247	likely_benign	0.2226	benign	-1.291	Destabilizing	0.013	N	0.127	neutral	None	None	None	None	I
L/C	0.6883	likely_pathogenic	0.6917	pathogenic	-0.782	Destabilizing	0.981	D	0.354	neutral	None	None	None	None	I
L/D	0.7777	likely_pathogenic	0.7662	pathogenic	-0.651	Destabilizing	0.704	D	0.381	neutral	None	None	None	None	I
L/E	0.4336	ambiguous	0.4278	ambiguous	-0.668	Destabilizing	0.704	D	0.363	neutral	None	None	None	None	I
L/F	0.2257	likely_benign	0.2204	benign	-0.85	Destabilizing	0.944	D	0.309	neutral	None	None	None	None	I
L/G	0.6069	likely_pathogenic	0.5879	pathogenic	-1.579	Destabilizing	0.329	N	0.35	neutral	None	None	None	None	I
L/H	0.3101	likely_benign	0.2977	benign	-0.684	Destabilizing	0.007	N	0.276	neutral	None	None	None	None	I
L/I	0.1364	likely_benign	0.1296	benign	-0.597	Destabilizing	0.27	N	0.198	neutral	N	0.43426484	None	None	I
L/K	0.3297	likely_benign	0.3118	benign	-0.873	Destabilizing	0.704	D	0.328	neutral	None	None	None	None	I
L/M	0.158	likely_benign	0.1481	benign	-0.497	Destabilizing	0.944	D	0.335	neutral	None	None	None	None	I
L/N	0.4894	ambiguous	0.4708	ambiguous	-0.701	Destabilizing	0.704	D	0.382	neutral	None	None	None	None	I
L/P	0.3139	likely_benign	0.3153	benign	-0.796	Destabilizing	0.006	N	0.279	neutral	N	0.346471556	None	None	I
L/Q	0.204	likely_benign	0.2093	benign	-0.878	Destabilizing	0.784	D	0.419	neutral	N	0.430166229	None	None	I
L/R	0.2358	likely_benign	0.2329	benign	-0.254	Destabilizing	0.642	D	0.38	neutral	N	0.393850087	None	None	I
L/S	0.307	likely_benign	0.2817	benign	-1.282	Destabilizing	0.013	N	0.157	neutral	None	None	None	None	I
L/T	0.2319	likely_benign	0.2006	benign	-1.184	Destabilizing	0.329	N	0.354	neutral	None	None	None	None	I
L/V	0.1099	likely_benign	0.1102	benign	-0.796	Destabilizing	0.002	N	0.121	neutral	N	0.378177128	None	None	I
L/W	0.3922	ambiguous	0.3766	ambiguous	-0.898	Destabilizing	0.995	D	0.345	neutral	None	None	None	None	I
L/Y	0.5028	ambiguous	0.4825	ambiguous	-0.681	Destabilizing	0.893	D	0.425	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.