TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19991	60196;60197;60198	chr2:178591848;178591847;178591846	chr2:179456575;179456574;179456573
N2AB	18350	55273;55274;55275	chr2:178591848;178591847;178591846	chr2:179456575;179456574;179456573
N2A	17423	52492;52493;52494	chr2:178591848;178591847;178591846	chr2:179456575;179456574;179456573
N2B	10926	33001;33002;33003	chr2:178591848;178591847;178591846	chr2:179456575;179456574;179456573
Novex-1	11051	33376;33377;33378	chr2:178591848;178591847;178591846	chr2:179456575;179456574;179456573
Novex-2	11118	33577;33578;33579	chr2:178591848;178591847;178591846	chr2:179456575;179456574;179456573
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-33
• Domain position: 15
• Structural Position: 17
• Q(SASA): 0.4411
• 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/Q	None	None	0.946	N	0.7	0.275	0.304760801415	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	0.4591	ambiguous	0.426	ambiguous	-0.15	Destabilizing	0.87	D	0.549	neutral	None	None	None	None	N
K/C	0.8287	likely_pathogenic	0.8348	pathogenic	-0.121	Destabilizing	0.998	D	0.796	deleterious	None	None	None	None	N
K/D	0.7532	likely_pathogenic	0.7153	pathogenic	-0.267	Destabilizing	0.959	D	0.738	prob.delet.	None	None	None	None	N
K/E	0.2797	likely_benign	0.2627	benign	-0.241	Destabilizing	0.716	D	0.481	neutral	N	0.499834326	None	None	N
K/F	0.9415	likely_pathogenic	0.9326	pathogenic	-0.225	Destabilizing	0.994	D	0.788	deleterious	None	None	None	None	N
K/G	0.6226	likely_pathogenic	0.5819	pathogenic	-0.424	Destabilizing	0.959	D	0.681	prob.neutral	None	None	None	None	N
K/H	0.515	ambiguous	0.4752	ambiguous	-0.878	Destabilizing	0.994	D	0.71	prob.delet.	None	None	None	None	N
K/I	0.6557	likely_pathogenic	0.6374	pathogenic	0.515	Stabilizing	0.979	D	0.801	deleterious	None	None	None	None	N
K/L	0.6457	likely_pathogenic	0.6236	pathogenic	0.515	Stabilizing	0.959	D	0.681	prob.neutral	None	None	None	None	N
K/M	0.4177	ambiguous	0.4	ambiguous	0.564	Stabilizing	0.998	D	0.713	prob.delet.	N	0.503235655	None	None	N
K/N	0.6383	likely_pathogenic	0.5943	pathogenic	0.071	Stabilizing	0.946	D	0.705	prob.neutral	N	0.505434934	None	None	N
K/P	0.8404	likely_pathogenic	0.8092	pathogenic	0.323	Stabilizing	0.979	D	0.723	prob.delet.	None	None	None	None	N
K/Q	0.191	likely_benign	0.1707	benign	-0.182	Destabilizing	0.946	D	0.7	prob.neutral	N	0.47012779	None	None	N
K/R	0.0999	likely_benign	0.0932	benign	-0.184	Destabilizing	0.035	N	0.301	neutral	N	0.503973496	None	None	N
K/S	0.5733	likely_pathogenic	0.5287	ambiguous	-0.436	Destabilizing	0.87	D	0.599	neutral	None	None	None	None	N
K/T	0.3621	ambiguous	0.3327	benign	-0.247	Destabilizing	0.946	D	0.693	prob.neutral	N	0.508512524	None	None	N
K/V	0.5798	likely_pathogenic	0.5641	pathogenic	0.323	Stabilizing	0.959	D	0.742	deleterious	None	None	None	None	N
K/W	0.9373	likely_pathogenic	0.9285	pathogenic	-0.157	Destabilizing	0.998	D	0.799	deleterious	None	None	None	None	N
K/Y	0.8472	likely_pathogenic	0.8292	pathogenic	0.183	Stabilizing	0.979	D	0.787	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.