TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6977	21154;21155;21156	chr2:178724446;178724445;178724444	chr2:179589173;179589172;179589171
N2AB	6660	20203;20204;20205	chr2:178724446;178724445;178724444	chr2:179589173;179589172;179589171
N2A	5733	17422;17423;17424	chr2:178724446;178724445;178724444	chr2:179589173;179589172;179589171
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-54
• Domain position: 30
• Structural Position: 44
• Q(SASA): 0.1578
• 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/H	None	None	1.0	D	0.683	0.639	0.887685046922	gnomAD-4.0.0	3.60097E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.9375E-06	0	0
L/P	rs1201922048	-1.684	1.0	N	0.765	0.538	0.768461157586	gnomAD-2.1.1	3.19E-05	None	None	None	None	I	None	1.14916E-04	0	None	0	0	None	0	None	0	0	0
L/P	rs1201922048	-1.684	1.0	N	0.765	0.538	0.768461157586	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
L/P	rs1201922048	-1.684	1.0	N	0.765	0.538	0.768461157586	gnomAD-4.0.0	6.57583E-06	None	None	None	None	I	None	2.41359E-05	0	None	0	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
L/A	0.834	likely_pathogenic	0.8276	pathogenic	-2.026	Highly Destabilizing	0.999	D	0.733	prob.delet.	None	None	None	None	I
L/C	0.9007	likely_pathogenic	0.903	pathogenic	-1.519	Destabilizing	1.0	D	0.663	neutral	None	None	None	None	I
L/D	0.9874	likely_pathogenic	0.9883	pathogenic	-1.126	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	I
L/E	0.9509	likely_pathogenic	0.9589	pathogenic	-1.048	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	I
L/F	0.5691	likely_pathogenic	0.6194	pathogenic	-1.31	Destabilizing	1.0	D	0.775	deleterious	N	0.508683962	None	None	I
L/G	0.9597	likely_pathogenic	0.9597	pathogenic	-2.438	Highly Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	I
L/H	0.9135	likely_pathogenic	0.9312	pathogenic	-1.579	Destabilizing	1.0	D	0.683	prob.neutral	D	0.531022103	None	None	I
L/I	0.172	likely_benign	0.1987	benign	-0.925	Destabilizing	0.999	D	0.604	neutral	N	0.472165801	None	None	I
L/K	0.925	likely_pathogenic	0.9386	pathogenic	-1.363	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	I
L/M	0.2944	likely_benign	0.3287	benign	-0.872	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	I
L/N	0.9301	likely_pathogenic	0.9357	pathogenic	-1.278	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	I
L/P	0.69	likely_pathogenic	0.6283	pathogenic	-1.262	Destabilizing	1.0	D	0.765	deleterious	N	0.361392237	None	None	I
L/Q	0.8682	likely_pathogenic	0.8971	pathogenic	-1.344	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	I
L/R	0.8786	likely_pathogenic	0.9055	pathogenic	-0.877	Destabilizing	1.0	D	0.766	deleterious	N	0.520074391	None	None	I
L/S	0.945	likely_pathogenic	0.9494	pathogenic	-2.069	Highly Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	I
L/T	0.841	likely_pathogenic	0.8515	pathogenic	-1.849	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	I
L/V	0.2477	likely_benign	0.2631	benign	-1.262	Destabilizing	0.999	D	0.554	neutral	N	0.48401759	None	None	I
L/W	0.8624	likely_pathogenic	0.8897	pathogenic	-1.369	Destabilizing	1.0	D	0.607	neutral	None	None	None	None	I
L/Y	0.8739	likely_pathogenic	0.8942	pathogenic	-1.159	Destabilizing	1.0	D	0.763	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.