TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17155	51688;51689;51690	chr2:178609960;178609959;178609958	chr2:179474687;179474686;179474685
N2AB	15514	46765;46766;46767	chr2:178609960;178609959;178609958	chr2:179474687;179474686;179474685
N2A	14587	43984;43985;43986	chr2:178609960;178609959;178609958	chr2:179474687;179474686;179474685
N2B	8090	24493;24494;24495	chr2:178609960;178609959;178609958	chr2:179474687;179474686;179474685
Novex-1	8215	24868;24869;24870	chr2:178609960;178609959;178609958	chr2:179474687;179474686;179474685
Novex-2	8282	25069;25070;25071	chr2:178609960;178609959;178609958	chr2:179474687;179474686;179474685
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: Fn3-13
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.3219
• 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	rs926188442	None	0.645	N	0.676	0.373	0.353974658523	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	0	9.57854E-04
E/G	rs926188442	None	0.645	N	0.676	0.373	0.353974658523	gnomAD-4.0.0	1.31638E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	9.57854E-04
E/V	None	None	0.864	N	0.753	0.393	0.414021929199	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.2901	likely_benign	0.2511	benign	-0.685	Destabilizing	0.477	N	0.58	neutral	N	0.47488274	None	None	N
E/C	0.9323	likely_pathogenic	0.9128	pathogenic	-0.36	Destabilizing	0.995	D	0.709	prob.delet.	None	None	None	None	N
E/D	0.3073	likely_benign	0.2639	benign	-0.773	Destabilizing	0.006	N	0.353	neutral	N	0.469722943	None	None	N
E/F	0.8969	likely_pathogenic	0.8616	pathogenic	-0.402	Destabilizing	0.995	D	0.776	deleterious	None	None	None	None	N
E/G	0.5029	ambiguous	0.4503	ambiguous	-0.969	Destabilizing	0.645	D	0.676	prob.neutral	N	0.483232069	None	None	N
E/H	0.7337	likely_pathogenic	0.6746	pathogenic	-0.518	Destabilizing	0.985	D	0.599	neutral	None	None	None	None	N
E/I	0.5119	ambiguous	0.4494	ambiguous	0.063	Stabilizing	0.945	D	0.789	deleterious	None	None	None	None	N
E/K	0.3943	ambiguous	0.3177	benign	-0.507	Destabilizing	0.006	N	0.393	neutral	N	0.477208182	None	None	N
E/L	0.6475	likely_pathogenic	0.5825	pathogenic	0.063	Stabilizing	0.894	D	0.762	deleterious	None	None	None	None	N
E/M	0.6076	likely_pathogenic	0.5669	pathogenic	0.321	Stabilizing	0.995	D	0.752	deleterious	None	None	None	None	N
E/N	0.5654	likely_pathogenic	0.4912	ambiguous	-0.743	Destabilizing	0.809	D	0.598	neutral	None	None	None	None	N
E/P	0.9937	likely_pathogenic	0.9908	pathogenic	-0.165	Destabilizing	0.945	D	0.772	deleterious	None	None	None	None	N
E/Q	0.2599	likely_benign	0.2219	benign	-0.658	Destabilizing	0.761	D	0.551	neutral	N	0.496564734	None	None	N
E/R	0.5533	ambiguous	0.4724	ambiguous	-0.214	Destabilizing	0.809	D	0.584	neutral	None	None	None	None	N
E/S	0.409	ambiguous	0.3577	ambiguous	-0.99	Destabilizing	0.547	D	0.483	neutral	None	None	None	None	N
E/T	0.347	ambiguous	0.3052	benign	-0.773	Destabilizing	0.894	D	0.722	prob.delet.	None	None	None	None	N
E/V	0.3074	likely_benign	0.2639	benign	-0.165	Destabilizing	0.864	D	0.753	deleterious	N	0.49167899	None	None	N
E/W	0.9754	likely_pathogenic	0.9656	pathogenic	-0.24	Destabilizing	0.995	D	0.691	prob.neutral	None	None	None	None	N
E/Y	0.8689	likely_pathogenic	0.8195	pathogenic	-0.198	Destabilizing	0.981	D	0.786	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.