TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2271	7036;7037;7038	chr2:178774453;178774452;178774451	chr2:179639180;179639179;179639178
N2AB	2271	7036;7037;7038	chr2:178774453;178774452;178774451	chr2:179639180;179639179;179639178
N2A	2271	7036;7037;7038	chr2:178774453;178774452;178774451	chr2:179639180;179639179;179639178
N2B	2225	6898;6899;6900	chr2:178774453;178774452;178774451	chr2:179639180;179639179;179639178
Novex-1	2225	6898;6899;6900	chr2:178774453;178774452;178774451	chr2:179639180;179639179;179639178
Novex-2	2225	6898;6899;6900	chr2:178774453;178774452;178774451	chr2:179639180;179639179;179639178
Novex-3	2271	7036;7037;7038	chr2:178774453;178774452;178774451	chr2:179639180;179639179;179639178

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-12
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.5954
• 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/R	None	None	0.999	N	0.544	0.354	0.409124616982	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
K/A	0.481	ambiguous	0.479	ambiguous	-0.46	Destabilizing	0.999	D	0.663	neutral	None	None	None	None	N
K/C	0.8358	likely_pathogenic	0.8312	pathogenic	-0.549	Destabilizing	1.0	D	0.668	neutral	None	None	None	None	N
K/D	0.6553	likely_pathogenic	0.6496	pathogenic	-0.224	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
K/E	0.1832	likely_benign	0.1841	benign	-0.097	Destabilizing	0.999	D	0.613	neutral	N	0.506196247	None	None	N
K/F	0.9078	likely_pathogenic	0.9054	pathogenic	-0.006	Destabilizing	1.0	D	0.66	neutral	None	None	None	None	N
K/G	0.6073	likely_pathogenic	0.5961	pathogenic	-0.841	Destabilizing	1.0	D	0.635	neutral	None	None	None	None	N
K/H	0.3892	ambiguous	0.3884	ambiguous	-1.09	Destabilizing	1.0	D	0.65	neutral	None	None	None	None	N
K/I	0.6073	likely_pathogenic	0.6106	pathogenic	0.532	Stabilizing	1.0	D	0.695	prob.neutral	D	0.528562943	None	None	N
K/L	0.5523	ambiguous	0.5547	ambiguous	0.532	Stabilizing	1.0	D	0.635	neutral	None	None	None	None	N
K/M	0.3858	ambiguous	0.3939	ambiguous	0.23	Stabilizing	1.0	D	0.642	neutral	None	None	None	None	N
K/N	0.4887	ambiguous	0.4874	ambiguous	-0.601	Destabilizing	1.0	D	0.708	prob.delet.	D	0.553641358	None	None	N
K/P	0.957	likely_pathogenic	0.9522	pathogenic	0.232	Stabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
K/Q	0.1484	likely_benign	0.1505	benign	-0.581	Destabilizing	1.0	D	0.684	prob.neutral	N	0.453205316	None	None	N
K/R	0.1088	likely_benign	0.1091	benign	-0.687	Destabilizing	0.999	D	0.544	neutral	N	0.50710526	None	None	N
K/S	0.4657	ambiguous	0.4611	ambiguous	-1.16	Destabilizing	0.999	D	0.643	neutral	None	None	None	None	N
K/T	0.2164	likely_benign	0.2186	benign	-0.828	Destabilizing	1.0	D	0.707	prob.neutral	N	0.50913584	None	None	N
K/V	0.5344	ambiguous	0.5365	ambiguous	0.232	Stabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
K/W	0.8921	likely_pathogenic	0.8896	pathogenic	0.052	Stabilizing	1.0	D	0.68	prob.neutral	None	None	None	None	N
K/Y	0.8134	likely_pathogenic	0.8109	pathogenic	0.323	Stabilizing	1.0	D	0.649	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.