TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26830	80713;80714;80715	chr2:178565644;178565643;178565642	chr2:179430371;179430370;179430369
N2AB	25189	75790;75791;75792	chr2:178565644;178565643;178565642	chr2:179430371;179430370;179430369
N2A	24262	73009;73010;73011	chr2:178565644;178565643;178565642	chr2:179430371;179430370;179430369
N2B	17765	53518;53519;53520	chr2:178565644;178565643;178565642	chr2:179430371;179430370;179430369
Novex-1	17890	53893;53894;53895	chr2:178565644;178565643;178565642	chr2:179430371;179430370;179430369
Novex-2	17957	54094;54095;54096	chr2:178565644;178565643;178565642	chr2:179430371;179430370;179430369
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Fn3-83
• Domain position: 51
• Structural Position: 68
• Q(SASA): 0.3017
• 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
V/L	None	None	0.472	N	0.464	0.263	0.431931272081	gnomAD-4.0.0	3.18322E-06	None	None	None	None	I	None	0	2.28655E-05	None	0	0	None	0	0	0	0	3.02554E-05

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
V/A	0.1156	likely_benign	0.1115	benign	-0.997	Destabilizing	0.004	N	0.153	neutral	N	0.487081246	None	None	I
V/C	0.6588	likely_pathogenic	0.6713	pathogenic	-0.847	Destabilizing	0.996	D	0.509	neutral	None	None	None	None	I
V/D	0.8083	likely_pathogenic	0.7957	pathogenic	-0.546	Destabilizing	0.91	D	0.596	neutral	None	None	None	None	I
V/E	0.7133	likely_pathogenic	0.6976	pathogenic	-0.55	Destabilizing	0.521	D	0.529	neutral	N	0.503209202	None	None	I
V/F	0.2786	likely_benign	0.2699	benign	-0.735	Destabilizing	0.984	D	0.535	neutral	None	None	None	None	I
V/G	0.2806	likely_benign	0.2838	benign	-1.283	Destabilizing	0.521	D	0.571	neutral	N	0.501767624	None	None	I
V/H	0.8135	likely_pathogenic	0.8095	pathogenic	-0.762	Destabilizing	0.987	D	0.609	neutral	None	None	None	None	I
V/I	0.103	likely_benign	0.0938	benign	-0.332	Destabilizing	0.706	D	0.496	neutral	None	None	None	None	I
V/K	0.7049	likely_pathogenic	0.7133	pathogenic	-0.848	Destabilizing	0.009	N	0.449	neutral	None	None	None	None	I
V/L	0.3479	ambiguous	0.3318	benign	-0.332	Destabilizing	0.472	N	0.464	neutral	N	0.500855833	None	None	I
V/M	0.2294	likely_benign	0.2063	benign	-0.411	Destabilizing	0.979	D	0.504	neutral	N	0.490664808	None	None	I
V/N	0.6729	likely_pathogenic	0.6452	pathogenic	-0.753	Destabilizing	0.91	D	0.611	neutral	None	None	None	None	I
V/P	0.7961	likely_pathogenic	0.7917	pathogenic	-0.517	Destabilizing	0.953	D	0.573	neutral	None	None	None	None	I
V/Q	0.6347	likely_pathogenic	0.6421	pathogenic	-0.854	Destabilizing	0.91	D	0.585	neutral	None	None	None	None	I
V/R	0.6377	likely_pathogenic	0.6571	pathogenic	-0.424	Destabilizing	0.835	D	0.6	neutral	None	None	None	None	I
V/S	0.2946	likely_benign	0.2834	benign	-1.261	Destabilizing	0.59	D	0.541	neutral	None	None	None	None	I
V/T	0.1989	likely_benign	0.1869	benign	-1.142	Destabilizing	0.742	D	0.471	neutral	None	None	None	None	I
V/W	0.927	likely_pathogenic	0.9237	pathogenic	-0.916	Destabilizing	0.996	D	0.68	prob.neutral	None	None	None	None	I
V/Y	0.743	likely_pathogenic	0.7473	pathogenic	-0.59	Destabilizing	0.984	D	0.538	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.