TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5659	17200;17201;17202	chr2:178731900;178731899;178731898	chr2:179596627;179596626;179596625
N2AB	5342	16249;16250;16251	chr2:178731900;178731899;178731898	chr2:179596627;179596626;179596625
N2A	4415	13468;13469;13470	chr2:178731900;178731899;178731898	chr2:179596627;179596626;179596625
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: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-40
• Domain position: 23
• Structural Position: 34
• Q(SASA): 0.4424
• 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/D	None	None	0.896	D	0.469	0.144	0.21279746466	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	6.07533E-05	0
E/K	rs763708860	-0.756	0.811	N	0.519	0.275	0.32580497728	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
E/K	rs763708860	-0.756	0.811	N	0.519	0.275	0.32580497728	gnomAD-3.1.2	1.31E-05	None	None	None	None	I	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
E/K	rs763708860	-0.756	0.811	N	0.519	0.275	0.32580497728	gnomAD-4.0.0	3.09866E-06	None	None	None	None	I	None	4.00545E-05	0	None	0	0	None	0	0	1.69531E-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	0.191	likely_benign	0.2179	benign	-0.976	Destabilizing	0.64	D	0.561	neutral	D	0.528056369	None	None	I
E/C	0.9009	likely_pathogenic	0.9246	pathogenic	-0.513	Destabilizing	0.999	D	0.711	prob.delet.	None	None	None	None	I
E/D	0.2616	likely_benign	0.2959	benign	-1.206	Destabilizing	0.896	D	0.469	neutral	D	0.530653957	None	None	I
E/F	0.8419	likely_pathogenic	0.8718	pathogenic	-0.512	Destabilizing	0.996	D	0.709	prob.delet.	None	None	None	None	I
E/G	0.2924	likely_benign	0.3489	ambiguous	-1.353	Destabilizing	0.026	N	0.425	neutral	N	0.487493663	None	None	I
E/H	0.4971	ambiguous	0.5587	ambiguous	-0.81	Destabilizing	0.988	D	0.582	neutral	None	None	None	None	I
E/I	0.4561	ambiguous	0.5118	ambiguous	0.059	Stabilizing	0.976	D	0.713	prob.delet.	None	None	None	None	I
E/K	0.1322	likely_benign	0.1652	benign	-0.696	Destabilizing	0.811	D	0.519	neutral	N	0.511316048	None	None	I
E/L	0.5002	ambiguous	0.5817	pathogenic	0.059	Stabilizing	0.976	D	0.685	prob.neutral	None	None	None	None	I
E/M	0.5103	ambiguous	0.5783	pathogenic	0.573	Stabilizing	0.999	D	0.695	prob.neutral	None	None	None	None	I
E/N	0.3698	ambiguous	0.4331	ambiguous	-1.136	Destabilizing	0.919	D	0.547	neutral	None	None	None	None	I
E/P	0.907	likely_pathogenic	0.9239	pathogenic	-0.265	Destabilizing	0.996	D	0.697	prob.neutral	None	None	None	None	I
E/Q	0.1337	likely_benign	0.153	benign	-1.004	Destabilizing	0.437	N	0.289	neutral	N	0.488305902	None	None	I
E/R	0.258	likely_benign	0.301	benign	-0.474	Destabilizing	0.976	D	0.569	neutral	None	None	None	None	I
E/S	0.2581	likely_benign	0.2937	benign	-1.516	Destabilizing	0.851	D	0.499	neutral	None	None	None	None	I
E/T	0.2641	likely_benign	0.2991	benign	-1.197	Destabilizing	0.132	N	0.382	neutral	None	None	None	None	I
E/V	0.2588	likely_benign	0.2976	benign	-0.265	Destabilizing	0.968	D	0.677	prob.neutral	D	0.523978701	None	None	I
E/W	0.9396	likely_pathogenic	0.9532	pathogenic	-0.291	Destabilizing	0.999	D	0.697	prob.neutral	None	None	None	None	I
E/Y	0.7372	likely_pathogenic	0.7919	pathogenic	-0.253	Destabilizing	0.996	D	0.705	prob.neutral	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.