TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25387	76384;76385;76386	chr2:178569973;178569972;178569971	chr2:179434700;179434699;179434698
N2AB	23746	71461;71462;71463	chr2:178569973;178569972;178569971	chr2:179434700;179434699;179434698
N2A	22819	68680;68681;68682	chr2:178569973;178569972;178569971	chr2:179434700;179434699;179434698
N2B	16322	49189;49190;49191	chr2:178569973;178569972;178569971	chr2:179434700;179434699;179434698
Novex-1	16447	49564;49565;49566	chr2:178569973;178569972;178569971	chr2:179434700;179434699;179434698
Novex-2	16514	49765;49766;49767	chr2:178569973;178569972;178569971	chr2:179434700;179434699;179434698
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Fn3-72
• Domain position: 84
• Structural Position: 117
• Q(SASA): 0.4126
• 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	rs879225322	None	0.942	N	0.691	0.186	None	gnomAD-3.1.2	1.32E-05	None	None	None	None	I	None	0	0	1.09649E-03	0	0	None	0	0	0	0	4.78011E-04
L/F	rs879225322	None	0.942	N	0.691	0.186	None	gnomAD-4.0.0	4.3417E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	4.241E-06	0	1.60267E-05
L/I	None	None	0.058	N	0.296	0.055	0.371344866733	gnomAD-4.0.0	6.84812E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.16063E-05	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	0.2023	likely_benign	0.2269	benign	-1.326	Destabilizing	0.559	D	0.637	neutral	None	None	None	None	I
L/C	0.3867	ambiguous	0.3992	ambiguous	-0.888	Destabilizing	0.998	D	0.732	prob.delet.	None	None	None	None	I
L/D	0.6659	likely_pathogenic	0.6528	pathogenic	-0.525	Destabilizing	0.993	D	0.803	deleterious	None	None	None	None	I
L/E	0.3921	ambiguous	0.387	ambiguous	-0.576	Destabilizing	0.978	D	0.8	deleterious	None	None	None	None	I
L/F	0.1189	likely_benign	0.1119	benign	-1.093	Destabilizing	0.942	D	0.691	prob.neutral	N	0.452176452	None	None	I
L/G	0.4847	ambiguous	0.503	ambiguous	-1.569	Destabilizing	0.978	D	0.796	deleterious	None	None	None	None	I
L/H	0.2422	likely_benign	0.2355	benign	-0.682	Destabilizing	0.997	D	0.808	deleterious	N	0.507549732	None	None	I
L/I	0.0756	likely_benign	0.0808	benign	-0.768	Destabilizing	0.058	N	0.296	neutral	N	0.400824912	None	None	I
L/K	0.2727	likely_benign	0.2771	benign	-0.666	Destabilizing	0.978	D	0.807	deleterious	None	None	None	None	I
L/M	0.1056	likely_benign	0.1169	benign	-0.571	Destabilizing	0.978	D	0.691	prob.neutral	None	None	None	None	I
L/N	0.3027	likely_benign	0.3137	benign	-0.455	Destabilizing	0.993	D	0.809	deleterious	None	None	None	None	I
L/P	0.2032	likely_benign	0.2246	benign	-0.921	Destabilizing	0.99	D	0.805	deleterious	N	0.456312835	None	None	I
L/Q	0.1662	likely_benign	0.17	benign	-0.717	Destabilizing	0.993	D	0.809	deleterious	None	None	None	None	I
L/R	0.2279	likely_benign	0.2125	benign	-0.041	Destabilizing	0.97	D	0.807	deleterious	N	0.460430576	None	None	I
L/S	0.2531	likely_benign	0.2649	benign	-1.08	Destabilizing	0.978	D	0.778	deleterious	None	None	None	None	I
L/T	0.1853	likely_benign	0.2043	benign	-1.019	Destabilizing	0.86	D	0.684	prob.neutral	None	None	None	None	I
L/V	0.0776	likely_benign	0.0835	benign	-0.921	Destabilizing	0.006	N	0.334	neutral	N	0.364845469	None	None	I
L/W	0.3061	likely_benign	0.2568	benign	-1.047	Destabilizing	0.998	D	0.801	deleterious	None	None	None	None	I
L/Y	0.3151	likely_benign	0.3106	benign	-0.819	Destabilizing	0.978	D	0.743	deleterious	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.