TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32088	96487;96488;96489	chr2:178543882;178543881;178543880	chr2:179408609;179408608;179408607
N2AB	30447	91564;91565;91566	chr2:178543882;178543881;178543880	chr2:179408609;179408608;179408607
N2A	29520	88783;88784;88785	chr2:178543882;178543881;178543880	chr2:179408609;179408608;179408607
N2B	23023	69292;69293;69294	chr2:178543882;178543881;178543880	chr2:179408609;179408608;179408607
Novex-1	23148	69667;69668;69669	chr2:178543882;178543881;178543880	chr2:179408609;179408608;179408607
Novex-2	23215	69868;69869;69870	chr2:178543882;178543881;178543880	chr2:179408609;179408608;179408607
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-153
• Domain position: 72
• Structural Position: 159
• Q(SASA): 0.4836
• 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
E/G	None	None	0.991	N	0.703	0.524	0.63538471256	gnomAD-4.0.0	1.59153E-06	None	None	None	None	N	None	0	0	None	0	2.77362E-05	None	0	0	0	0	0
E/K	rs1351862807	0.08	0.969	D	0.679	0.389	0.470730462751	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
E/K	rs1351862807	0.08	0.969	D	0.679	0.389	0.470730462751	gnomAD-4.0.0	1.59156E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43287E-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
E/A	0.1511	likely_benign	0.1442	benign	-0.58	Destabilizing	0.885	D	0.627	neutral	N	0.497417937	None	None	N
E/C	0.766	likely_pathogenic	0.7469	pathogenic	0.004	Stabilizing	0.999	D	0.82	deleterious	None	None	None	None	N
E/D	0.3378	likely_benign	0.3162	benign	-0.689	Destabilizing	0.99	D	0.555	neutral	N	0.499583984	None	None	N
E/F	0.729	likely_pathogenic	0.7058	pathogenic	-0.635	Destabilizing	0.993	D	0.807	deleterious	None	None	None	None	N
E/G	0.2588	likely_benign	0.2397	benign	-0.822	Destabilizing	0.991	D	0.703	prob.neutral	N	0.513675767	None	None	N
E/H	0.4515	ambiguous	0.4293	ambiguous	-0.829	Destabilizing	0.999	D	0.727	prob.delet.	None	None	None	None	N
E/I	0.254	likely_benign	0.2422	benign	0.04	Stabilizing	0.973	D	0.723	prob.delet.	None	None	None	None	N
E/K	0.1328	likely_benign	0.127	benign	0.07	Stabilizing	0.969	D	0.679	prob.neutral	D	0.52711222	None	None	N
E/L	0.4108	ambiguous	0.3793	ambiguous	0.04	Stabilizing	0.91	D	0.722	prob.delet.	None	None	None	None	N
E/M	0.3574	ambiguous	0.3362	benign	0.437	Stabilizing	0.998	D	0.795	deleterious	None	None	None	None	N
E/N	0.3368	likely_benign	0.3204	benign	-0.189	Destabilizing	0.998	D	0.745	deleterious	None	None	None	None	N
E/P	0.9902	likely_pathogenic	0.986	pathogenic	-0.146	Destabilizing	0.998	D	0.765	deleterious	None	None	None	None	N
E/Q	0.1049	likely_benign	0.1018	benign	-0.169	Destabilizing	0.997	D	0.694	prob.neutral	N	0.519783603	None	None	N
E/R	0.243	likely_benign	0.2261	benign	0.102	Stabilizing	0.998	D	0.753	deleterious	None	None	None	None	N
E/S	0.1831	likely_benign	0.1745	benign	-0.398	Destabilizing	0.976	D	0.721	prob.delet.	None	None	None	None	N
E/T	0.1611	likely_benign	0.1559	benign	-0.203	Destabilizing	0.986	D	0.712	prob.delet.	None	None	None	None	N
E/V	0.1397	likely_benign	0.1375	benign	-0.146	Destabilizing	0.1	N	0.496	neutral	N	0.495545059	None	None	N
E/W	0.8996	likely_pathogenic	0.881	pathogenic	-0.528	Destabilizing	0.999	D	0.798	deleterious	None	None	None	None	N
E/Y	0.6797	likely_pathogenic	0.6486	pathogenic	-0.397	Destabilizing	0.998	D	0.807	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.