TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1164	3715;3716;3717	chr2:178781154;178781153;178781152	chr2:179645881;179645880;179645879
N2AB	1164	3715;3716;3717	chr2:178781154;178781153;178781152	chr2:179645881;179645880;179645879
N2A	1164	3715;3716;3717	chr2:178781154;178781153;178781152	chr2:179645881;179645880;179645879
N2B	1118	3577;3578;3579	chr2:178781154;178781153;178781152	chr2:179645881;179645880;179645879
Novex-1	1118	3577;3578;3579	chr2:178781154;178781153;178781152	chr2:179645881;179645880;179645879
Novex-2	1118	3577;3578;3579	chr2:178781154;178781153;178781152	chr2:179645881;179645880;179645879
Novex-3	1164	3715;3716;3717	chr2:178781154;178781153;178781152	chr2:179645881;179645880;179645879

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-4
• Domain position: 83
• Structural Position: 165
• Q(SASA): 0.5786
• 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
E/K	None	None	0.998	N	0.653	0.534	0.372268306217	gnomAD-4.0.0	1.59081E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43275E-05	0
E/V	None	None	1.0	N	0.724	0.729	0.588653130956	gnomAD-4.0.0	1.59078E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.8569E-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
E/A	0.6775	likely_pathogenic	0.6479	pathogenic	-0.819	Destabilizing	0.998	D	0.677	prob.neutral	N	0.51641753	None	None	I
E/C	0.9924	likely_pathogenic	0.9906	pathogenic	-0.409	Destabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	I
E/D	0.6551	likely_pathogenic	0.6452	pathogenic	-0.798	Destabilizing	0.434	N	0.227	neutral	N	0.50625099	None	None	I
E/F	0.9806	likely_pathogenic	0.9768	pathogenic	-0.339	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	I
E/G	0.7994	likely_pathogenic	0.7834	pathogenic	-1.109	Destabilizing	0.999	D	0.657	neutral	D	0.602682885	None	None	I
E/H	0.9545	likely_pathogenic	0.9495	pathogenic	-0.257	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	I
E/I	0.8782	likely_pathogenic	0.8608	pathogenic	-0.049	Destabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	I
E/K	0.7306	likely_pathogenic	0.7031	pathogenic	-0.189	Destabilizing	0.998	D	0.653	neutral	N	0.501177259	None	None	I
E/L	0.9417	likely_pathogenic	0.9261	pathogenic	-0.049	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	I
E/M	0.8879	likely_pathogenic	0.8641	pathogenic	0.191	Stabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	I
E/N	0.8713	likely_pathogenic	0.8667	pathogenic	-0.714	Destabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	I
E/P	0.9978	likely_pathogenic	0.9979	pathogenic	-0.286	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	I
E/Q	0.4954	ambiguous	0.4954	ambiguous	-0.64	Destabilizing	0.999	D	0.656	neutral	N	0.502714098	None	None	I
E/R	0.8817	likely_pathogenic	0.8787	pathogenic	0.169	Stabilizing	1.0	D	0.749	deleterious	None	None	None	None	I
E/S	0.7233	likely_pathogenic	0.707	pathogenic	-0.924	Destabilizing	0.997	D	0.679	prob.neutral	None	None	None	None	I
E/T	0.7786	likely_pathogenic	0.7492	pathogenic	-0.682	Destabilizing	1.0	D	0.657	neutral	None	None	None	None	I
E/V	0.7302	likely_pathogenic	0.6909	pathogenic	-0.286	Destabilizing	1.0	D	0.724	prob.delet.	N	0.517252786	None	None	I
E/W	0.9969	likely_pathogenic	0.9963	pathogenic	-0.038	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	I
E/Y	0.9792	likely_pathogenic	0.9755	pathogenic	-0.067	Destabilizing	1.0	D	0.724	prob.delet.	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.