TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25777	77554;77555;77556	chr2:178568803;178568802;178568801	chr2:179433530;179433529;179433528
N2AB	24136	72631;72632;72633	chr2:178568803;178568802;178568801	chr2:179433530;179433529;179433528
N2A	23209	69850;69851;69852	chr2:178568803;178568802;178568801	chr2:179433530;179433529;179433528
N2B	16712	50359;50360;50361	chr2:178568803;178568802;178568801	chr2:179433530;179433529;179433528
Novex-1	16837	50734;50735;50736	chr2:178568803;178568802;178568801	chr2:179433530;179433529;179433528
Novex-2	16904	50935;50936;50937	chr2:178568803;178568802;178568801	chr2:179433530;179433529;179433528
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-75
• Domain position: 80
• Structural Position: 114
• Q(SASA): 0.406
• 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
K/E	rs778484596	0.267	0.994	N	0.643	0.482	0.373537453441	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.94E-06	0
K/E	rs778484596	0.267	0.994	N	0.643	0.482	0.373537453441	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
K/E	rs778484596	0.267	0.994	N	0.643	0.482	0.373537453441	gnomAD-4.0.0	6.81906E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.07126E-05	0	4.80523E-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
K/A	0.5807	likely_pathogenic	0.6002	pathogenic	0.035	Stabilizing	0.999	D	0.679	prob.neutral	None	None	None	None	I
K/C	0.7518	likely_pathogenic	0.7587	pathogenic	-0.267	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	I
K/D	0.9453	likely_pathogenic	0.9484	pathogenic	-0.089	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	I
K/E	0.564	likely_pathogenic	0.6024	pathogenic	-0.094	Destabilizing	0.994	D	0.643	neutral	N	0.490870913	None	None	I
K/F	0.864	likely_pathogenic	0.8679	pathogenic	-0.226	Destabilizing	1.0	D	0.782	deleterious	None	None	None	None	I
K/G	0.8359	likely_pathogenic	0.8449	pathogenic	-0.135	Destabilizing	1.0	D	0.71	prob.delet.	None	None	None	None	I
K/H	0.4731	ambiguous	0.4817	ambiguous	-0.316	Destabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	I
K/I	0.5041	ambiguous	0.5503	ambiguous	0.4	Stabilizing	0.986	D	0.787	deleterious	None	None	None	None	I
K/L	0.6141	likely_pathogenic	0.6214	pathogenic	0.4	Stabilizing	0.986	D	0.71	prob.delet.	None	None	None	None	I
K/M	0.3423	ambiguous	0.3443	ambiguous	0.144	Stabilizing	0.999	D	0.726	prob.delet.	D	0.525735635	None	None	I
K/N	0.6898	likely_pathogenic	0.7156	pathogenic	0.199	Stabilizing	0.999	D	0.775	deleterious	N	0.512574337	None	None	I
K/P	0.9891	likely_pathogenic	0.9894	pathogenic	0.305	Stabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	I
K/Q	0.2893	likely_benign	0.2985	benign	0.013	Stabilizing	0.996	D	0.768	deleterious	N	0.496412806	None	None	I
K/R	0.1079	likely_benign	0.1088	benign	0.011	Stabilizing	0.99	D	0.585	neutral	N	0.515171925	None	None	I
K/S	0.7635	likely_pathogenic	0.776	pathogenic	-0.245	Destabilizing	0.999	D	0.733	prob.delet.	None	None	None	None	I
K/T	0.4736	ambiguous	0.4954	ambiguous	-0.115	Destabilizing	0.998	D	0.728	prob.delet.	N	0.51830823	None	None	I
K/V	0.4503	ambiguous	0.4747	ambiguous	0.305	Stabilizing	0.99	D	0.752	deleterious	None	None	None	None	I
K/W	0.9045	likely_pathogenic	0.9078	pathogenic	-0.265	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	I
K/Y	0.7226	likely_pathogenic	0.7175	pathogenic	0.09	Stabilizing	0.998	D	0.774	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.