TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9763	29512;29513;29514	chr2:178706587;178706586;178706585	chr2:179571314;179571313;179571312
N2AB	9446	28561;28562;28563	chr2:178706587;178706586;178706585	chr2:179571314;179571313;179571312
N2A	8519	25780;25781;25782	chr2:178706587;178706586;178706585	chr2:179571314;179571313;179571312
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: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-83
• Domain position: 66
• Structural Position: 146
• Q(SASA): 0.7347
• 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
K/E	rs1414221406	None	0.996	None	0.483	0.295	0.244539031024	gnomAD-4.0.0	1.59099E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8578E-06	0	0
K/N	rs1301356747	0.526	0.999	None	0.607	0.197	0.117506650769	gnomAD-2.1.1	4.01E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.85E-06	0
K/N	rs1301356747	0.526	0.999	None	0.607	0.197	0.117506650769	gnomAD-4.0.0	3.18214E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85801E-06	0	3.02352E-05

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
K/A	0.8724	likely_pathogenic	0.6442	pathogenic	-0.116	Destabilizing	0.998	D	0.542	neutral	None	None	None	None	N
K/C	0.9877	likely_pathogenic	0.9519	pathogenic	-0.21	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
K/D	0.9793	likely_pathogenic	0.9108	pathogenic	0.05	Stabilizing	1.0	D	0.634	neutral	None	None	None	None	N
K/E	0.8232	likely_pathogenic	0.4981	ambiguous	0.057	Stabilizing	0.996	D	0.483	neutral	None	None	None	None	N
K/F	0.9893	likely_pathogenic	0.9509	pathogenic	-0.312	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
K/G	0.9306	likely_pathogenic	0.7676	pathogenic	-0.336	Destabilizing	1.0	D	0.518	neutral	None	None	None	None	N
K/H	0.8767	likely_pathogenic	0.7147	pathogenic	-0.694	Destabilizing	1.0	D	0.656	neutral	None	None	None	None	N
K/I	0.9117	likely_pathogenic	0.6862	pathogenic	0.387	Stabilizing	1.0	D	0.702	prob.neutral	None	None	None	None	N
K/L	0.8728	likely_pathogenic	0.661	pathogenic	0.387	Stabilizing	1.0	D	0.518	neutral	None	None	None	None	N
K/M	0.8451	likely_pathogenic	0.5638	ambiguous	0.339	Stabilizing	1.0	D	0.661	neutral	None	None	None	None	N
K/N	0.9503	likely_pathogenic	0.8083	pathogenic	0.175	Stabilizing	0.999	D	0.607	neutral	None	None	None	None	N
K/P	0.926	likely_pathogenic	0.8043	pathogenic	0.248	Stabilizing	1.0	D	0.632	neutral	None	None	None	None	N
K/Q	0.6095	likely_pathogenic	0.3493	ambiguous	-0.056	Destabilizing	0.999	D	0.599	neutral	None	None	None	None	N
K/R	0.1278	likely_benign	0.0986	benign	-0.089	Destabilizing	0.64	D	0.308	neutral	None	None	None	None	N
K/S	0.9317	likely_pathogenic	0.7645	pathogenic	-0.372	Destabilizing	0.998	D	0.527	neutral	None	None	None	None	N
K/T	0.8307	likely_pathogenic	0.5293	ambiguous	-0.21	Destabilizing	0.999	D	0.588	neutral	None	None	None	None	N
K/V	0.8601	likely_pathogenic	0.6251	pathogenic	0.248	Stabilizing	1.0	D	0.631	neutral	None	None	None	None	N
K/W	0.9853	likely_pathogenic	0.9473	pathogenic	-0.266	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
K/Y	0.974	likely_pathogenic	0.9097	pathogenic	0.083	Stabilizing	1.0	D	0.665	neutral	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.