TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4762	14509;14510;14511	chr2:178738169;178738168;178738167	chr2:179602896;179602895;179602894
N2AB	4445	13558;13559;13560	chr2:178738169;178738168;178738167	chr2:179602896;179602895;179602894
N2A	3518	10777;10778;10779	chr2:178738169;178738168;178738167	chr2:179602896;179602895;179602894
N2B	4399	13420;13421;13422	chr2:178738169;178738168;178738167	chr2:179602896;179602895;179602894
Novex-1	4524	13795;13796;13797	chr2:178738169;178738168;178738167	chr2:179602896;179602895;179602894
Novex-2	4591	13996;13997;13998	chr2:178738169;178738168;178738167	chr2:179602896;179602895;179602894
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-30
• Domain position: 63
• Structural Position: 144
• Q(SASA): 0.145
• 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
T/I	rs2081863914	None	0.934	N	0.55	0.346	0.453679287548	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
T/P	rs1439059332	None	0.002	N	0.248	0.349	0.28297238246	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
T/P	rs1439059332	None	0.002	N	0.248	0.349	0.28297238246	gnomAD-4.0.0	1.85937E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.54289E-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
T/A	0.1766	likely_benign	0.1718	benign	-1.075	Destabilizing	0.005	N	0.152	neutral	N	0.450753441	None	None	I
T/C	0.5666	likely_pathogenic	0.5756	pathogenic	-1.312	Destabilizing	0.998	D	0.509	neutral	None	None	None	None	I
T/D	0.9841	likely_pathogenic	0.9757	pathogenic	-2.261	Highly Destabilizing	0.915	D	0.509	neutral	None	None	None	None	I
T/E	0.9695	likely_pathogenic	0.963	pathogenic	-2.11	Highly Destabilizing	0.842	D	0.493	neutral	None	None	None	None	I
T/F	0.9732	likely_pathogenic	0.9643	pathogenic	-0.939	Destabilizing	0.991	D	0.539	neutral	None	None	None	None	I
T/G	0.7472	likely_pathogenic	0.7155	pathogenic	-1.404	Destabilizing	0.728	D	0.397	neutral	None	None	None	None	I
T/H	0.9613	likely_pathogenic	0.9477	pathogenic	-1.542	Destabilizing	0.998	D	0.515	neutral	None	None	None	None	I
T/I	0.7429	likely_pathogenic	0.6856	pathogenic	-0.242	Destabilizing	0.934	D	0.55	neutral	N	0.471325082	None	None	I
T/K	0.9696	likely_pathogenic	0.9656	pathogenic	-0.871	Destabilizing	0.842	D	0.501	neutral	None	None	None	None	I
T/L	0.4012	ambiguous	0.4109	ambiguous	-0.242	Destabilizing	0.842	D	0.418	neutral	None	None	None	None	I
T/M	0.3938	ambiguous	0.3727	ambiguous	-0.276	Destabilizing	0.998	D	0.523	neutral	None	None	None	None	I
T/N	0.7494	likely_pathogenic	0.6566	pathogenic	-1.561	Destabilizing	0.966	D	0.519	neutral	N	0.478735164	None	None	I
T/P	0.261	likely_benign	0.2145	benign	-0.49	Destabilizing	0.002	N	0.248	neutral	N	0.478735164	None	None	I
T/Q	0.938	likely_pathogenic	0.9301	pathogenic	-1.524	Destabilizing	0.974	D	0.541	neutral	None	None	None	None	I
T/R	0.9564	likely_pathogenic	0.9509	pathogenic	-0.837	Destabilizing	0.974	D	0.548	neutral	None	None	None	None	I
T/S	0.3477	ambiguous	0.278	benign	-1.621	Destabilizing	0.454	N	0.43	neutral	N	0.477807057	None	None	I
T/V	0.4134	ambiguous	0.4206	ambiguous	-0.49	Destabilizing	0.728	D	0.395	neutral	None	None	None	None	I
T/W	0.9951	likely_pathogenic	0.9935	pathogenic	-1.115	Destabilizing	0.998	D	0.543	neutral	None	None	None	None	I
T/Y	0.9799	likely_pathogenic	0.9728	pathogenic	-0.715	Destabilizing	0.991	D	0.541	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.