TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5156	15691;15692;15693	chr2:178734358;178734357;178734356	chr2:179599085;179599084;179599083
N2AB	4839	14740;14741;14742	chr2:178734358;178734357;178734356	chr2:179599085;179599084;179599083
N2A	3912	11959;11960;11961	chr2:178734358;178734357;178734356	chr2:179599085;179599084;179599083
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: C
• RefSeq wild type transcript codon: TGT
• RefSeq wild type template codon: ACA
• Domain: Ig-34
• Domain position: 82
• Structural Position: 166
• Q(SASA): 0.1686
• 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
C/Y	None	None	0.996	D	0.663	0.402	0.770558164856	gnomAD-4.0.0	3.60097E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.625E-06	6.07533E-05	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
C/A	0.2378	likely_benign	0.2597	benign	-1.312	Destabilizing	0.863	D	0.383	neutral	None	None	None	None	I
C/D	0.3638	ambiguous	0.4859	ambiguous	0.22	Stabilizing	0.884	D	0.66	neutral	None	None	None	None	I
C/E	0.602	likely_pathogenic	0.6717	pathogenic	0.286	Stabilizing	0.939	D	0.695	prob.neutral	None	None	None	None	I
C/F	0.2548	likely_benign	0.3003	benign	-0.762	Destabilizing	0.996	D	0.662	neutral	D	0.573970628	None	None	I
C/G	0.1516	likely_benign	0.1776	benign	-1.577	Destabilizing	0.015	N	0.402	neutral	N	0.508140706	None	None	I
C/H	0.4384	ambiguous	0.4947	ambiguous	-1.434	Destabilizing	0.991	D	0.671	neutral	None	None	None	None	I
C/I	0.3752	ambiguous	0.4032	ambiguous	-0.655	Destabilizing	0.997	D	0.603	neutral	None	None	None	None	I
C/K	0.6938	likely_pathogenic	0.7208	pathogenic	-0.55	Destabilizing	0.939	D	0.683	prob.neutral	None	None	None	None	I
C/L	0.4766	ambiguous	0.505	ambiguous	-0.655	Destabilizing	0.969	D	0.554	neutral	None	None	None	None	I
C/M	0.5527	ambiguous	0.594	pathogenic	0.061	Stabilizing	0.997	D	0.562	neutral	None	None	None	None	I
C/N	0.3689	ambiguous	0.4437	ambiguous	-0.466	Destabilizing	0.079	N	0.403	neutral	None	None	None	None	I
C/P	0.9755	likely_pathogenic	0.9827	pathogenic	-0.847	Destabilizing	0.997	D	0.693	prob.neutral	None	None	None	None	I
C/Q	0.4746	ambiguous	0.5018	ambiguous	-0.412	Destabilizing	0.991	D	0.693	prob.neutral	None	None	None	None	I
C/R	0.3939	ambiguous	0.3992	ambiguous	-0.333	Destabilizing	0.988	D	0.697	prob.neutral	N	0.50516102	None	None	I
C/S	0.1684	likely_benign	0.198	benign	-1.022	Destabilizing	0.826	D	0.501	neutral	N	0.470705775	None	None	I
C/T	0.2573	likely_benign	0.2774	benign	-0.783	Destabilizing	0.939	D	0.554	neutral	None	None	None	None	I
C/V	0.2979	likely_benign	0.3042	benign	-0.847	Destabilizing	0.99	D	0.563	neutral	None	None	None	None	I
C/W	0.5465	ambiguous	0.6218	pathogenic	-0.728	Destabilizing	0.999	D	0.641	neutral	D	0.575136469	None	None	I
C/Y	0.3174	likely_benign	0.3676	ambiguous	-0.698	Destabilizing	0.996	D	0.663	neutral	D	0.573818206	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.