TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5414	16465;16466;16467	chr2:178732936;178732935;178732934	chr2:179597663;179597662;179597661
N2AB	5097	15514;15515;15516	chr2:178732936;178732935;178732934	chr2:179597663;179597662;179597661
N2A	4170	12733;12734;12735	chr2:178732936;178732935;178732934	chr2:179597663;179597662;179597661
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: TTG
• RefSeq wild type template codon: AAC
• Domain: Ig-37
• Domain position: 58
• Structural Position: 138
• Q(SASA): 0.0681
• Predicted PPI site: N

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/S	rs764508505	-3.247	0.997	D	0.893	0.774	0.910103704093	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	1.68312E-04	None	0	None	0	0	0
L/S	rs764508505	-3.247	0.997	D	0.893	0.774	0.910103704093	gnomAD-4.0.0	1.36864E-06	None	None	None	None	N	None	0	0	None	0	5.05306E-05	None	0	0	0	0	0
L/W	rs764508505	None	1.0	D	0.874	0.793	0.90289129007	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
L/W	rs764508505	None	1.0	D	0.874	0.793	0.90289129007	gnomAD-4.0.0	1.8594E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.69529E-06	0	1.60169E-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
L/A	0.8488	likely_pathogenic	0.8748	pathogenic	-2.162	Highly Destabilizing	0.983	D	0.751	deleterious	None	None	None	None	N
L/C	0.8815	likely_pathogenic	0.9018	pathogenic	-1.437	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
L/D	0.9994	likely_pathogenic	0.9996	pathogenic	-3.006	Highly Destabilizing	0.999	D	0.921	deleterious	None	None	None	None	N
L/E	0.994	likely_pathogenic	0.9953	pathogenic	-2.682	Highly Destabilizing	0.998	D	0.899	deleterious	None	None	None	None	N
L/F	0.5491	ambiguous	0.6279	pathogenic	-1.376	Destabilizing	0.993	D	0.772	deleterious	D	0.551159087	None	None	N
L/G	0.976	likely_pathogenic	0.9816	pathogenic	-2.761	Highly Destabilizing	0.998	D	0.897	deleterious	None	None	None	None	N
L/H	0.9852	likely_pathogenic	0.9896	pathogenic	-2.733	Highly Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
L/I	0.2669	likely_benign	0.2793	benign	-0.367	Destabilizing	0.966	D	0.653	neutral	None	None	None	None	N
L/K	0.9911	likely_pathogenic	0.9928	pathogenic	-1.592	Destabilizing	0.998	D	0.897	deleterious	None	None	None	None	N
L/M	0.2083	likely_benign	0.2355	benign	-0.578	Destabilizing	0.898	D	0.588	neutral	D	0.536030573	None	None	N
L/N	0.9958	likely_pathogenic	0.9969	pathogenic	-2.339	Highly Destabilizing	0.999	D	0.919	deleterious	None	None	None	None	N
L/P	0.9971	likely_pathogenic	0.9975	pathogenic	-0.955	Destabilizing	0.999	D	0.917	deleterious	None	None	None	None	N
L/Q	0.9674	likely_pathogenic	0.9751	pathogenic	-1.937	Destabilizing	0.998	D	0.919	deleterious	None	None	None	None	N
L/R	0.9753	likely_pathogenic	0.9804	pathogenic	-1.872	Destabilizing	0.998	D	0.901	deleterious	None	None	None	None	N
L/S	0.9806	likely_pathogenic	0.9866	pathogenic	-2.834	Highly Destabilizing	0.997	D	0.893	deleterious	D	0.579685049	None	None	N
L/T	0.9376	likely_pathogenic	0.9525	pathogenic	-2.337	Highly Destabilizing	0.995	D	0.805	deleterious	None	None	None	None	N
L/V	0.2646	likely_benign	0.2756	benign	-0.955	Destabilizing	0.955	D	0.681	prob.neutral	D	0.555198012	None	None	N
L/W	0.9478	likely_pathogenic	0.9697	pathogenic	-1.822	Destabilizing	1.0	D	0.874	deleterious	D	0.579685049	None	None	N
L/Y	0.9613	likely_pathogenic	0.9743	pathogenic	-1.515	Destabilizing	0.998	D	0.849	deleterious	None	None	None	None	N

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.