TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19634	59125;59126;59127	chr2:178593308;178593307;178593306	chr2:179458035;179458034;179458033
N2AB	17993	54202;54203;54204	chr2:178593308;178593307;178593306	chr2:179458035;179458034;179458033
N2A	17066	51421;51422;51423	chr2:178593308;178593307;178593306	chr2:179458035;179458034;179458033
N2B	10569	31930;31931;31932	chr2:178593308;178593307;178593306	chr2:179458035;179458034;179458033
Novex-1	10694	32305;32306;32307	chr2:178593308;178593307;178593306	chr2:179458035;179458034;179458033
Novex-2	10761	32506;32507;32508	chr2:178593308;178593307;178593306	chr2:179458035;179458034;179458033
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Fn3-30
• Domain position: 56
• Structural Position: 82
• Q(SASA): 0.583
• 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
H/Q	rs397517639	0.066	0.989	N	0.449	0.218	0.201204373187	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	9.94E-05	0	None	0	None	0	0	0
H/Q	rs397517639	0.066	0.989	N	0.449	0.218	0.201204373187	gnomAD-4.0.0	1.59196E-06	None	None	None	None	I	None	0	0	None	4.76963E-05	0	None	0	0	0	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
H/A	0.3182	likely_benign	0.3284	benign	-0.78	Destabilizing	0.842	D	0.479	neutral	None	None	None	None	I
H/C	0.1821	likely_benign	0.1953	benign	0.091	Stabilizing	0.998	D	0.477	neutral	None	None	None	None	I
H/D	0.3364	likely_benign	0.3581	ambiguous	-0.876	Destabilizing	0.989	D	0.471	neutral	N	0.470226282	None	None	I
H/E	0.4001	ambiguous	0.4273	ambiguous	-0.746	Destabilizing	0.915	D	0.426	neutral	None	None	None	None	I
H/F	0.1677	likely_benign	0.1876	benign	0.733	Stabilizing	0.007	N	0.188	neutral	None	None	None	None	I
H/G	0.3951	ambiguous	0.4139	ambiguous	-1.173	Destabilizing	0.915	D	0.479	neutral	None	None	None	None	I
H/I	0.2522	likely_benign	0.2712	benign	0.327	Stabilizing	0.904	D	0.478	neutral	None	None	None	None	I
H/K	0.388	ambiguous	0.417	ambiguous	-0.541	Destabilizing	0.974	D	0.473	neutral	None	None	None	None	I
H/L	0.1278	likely_benign	0.1293	benign	0.327	Stabilizing	0.669	D	0.489	neutral	N	0.419605461	None	None	I
H/M	0.4293	ambiguous	0.4571	ambiguous	0.137	Stabilizing	0.993	D	0.462	neutral	None	None	None	None	I
H/N	0.1288	likely_benign	0.1303	benign	-0.87	Destabilizing	0.891	D	0.463	neutral	N	0.441847602	None	None	I
H/P	0.2456	likely_benign	0.2579	benign	-0.023	Destabilizing	0.989	D	0.493	neutral	N	0.451120446	None	None	I
H/Q	0.2479	likely_benign	0.262	benign	-0.572	Destabilizing	0.989	D	0.449	neutral	N	0.50958996	None	None	I
H/R	0.2032	likely_benign	0.2184	benign	-1.137	Destabilizing	0.966	D	0.432	neutral	N	0.439268657	None	None	I
H/S	0.2179	likely_benign	0.2225	benign	-0.787	Destabilizing	0.915	D	0.455	neutral	None	None	None	None	I
H/T	0.2882	likely_benign	0.3024	benign	-0.547	Destabilizing	0.974	D	0.479	neutral	None	None	None	None	I
H/V	0.2426	likely_benign	0.2578	benign	-0.023	Destabilizing	0.842	D	0.479	neutral	None	None	None	None	I
H/W	0.3224	likely_benign	0.366	ambiguous	1.082	Stabilizing	0.993	D	0.455	neutral	None	None	None	None	I
H/Y	0.0629	likely_benign	0.0689	benign	1.059	Stabilizing	0.012	N	0.107	neutral	N	0.441116883	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.