TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34297	103114;103115;103116	chr2:178533726;178533725;178533724	chr2:179398453;179398452;179398451
N2AB	32656	98191;98192;98193	chr2:178533726;178533725;178533724	chr2:179398453;179398452;179398451
N2A	31729	95410;95411;95412	chr2:178533726;178533725;178533724	chr2:179398453;179398452;179398451
N2B	25232	75919;75920;75921	chr2:178533726;178533725;178533724	chr2:179398453;179398452;179398451
Novex-1	25357	76294;76295;76296	chr2:178533726;178533725;178533724	chr2:179398453;179398452;179398451
Novex-2	25424	76495;76496;76497	chr2:178533726;178533725;178533724	chr2:179398453;179398452;179398451
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-161
• Domain position: 40
• Structural Position: 56
• Q(SASA): 0.6789
• 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/N	rs1019464699	0.058	0.982	N	0.672	0.347	0.29132392195	gnomAD-2.1.1	3.18E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
K/N	rs1019464699	0.058	0.982	N	0.672	0.347	0.29132392195	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
K/N	rs1019464699	0.058	0.982	N	0.672	0.347	0.29132392195	gnomAD-4.0.0	2.02984E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.40981E-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	0.468	ambiguous	0.4841	ambiguous	-0.383	Destabilizing	0.953	D	0.599	neutral	None	None	None	None	N
K/C	0.7672	likely_pathogenic	0.82	pathogenic	-0.414	Destabilizing	0.999	D	0.733	prob.delet.	None	None	None	None	N
K/D	0.8088	likely_pathogenic	0.8464	pathogenic	0.012	Stabilizing	0.993	D	0.704	prob.neutral	None	None	None	None	N
K/E	0.2519	likely_benign	0.2945	benign	0.117	Stabilizing	0.939	D	0.601	neutral	N	0.429334957	None	None	N
K/F	0.8668	likely_pathogenic	0.9013	pathogenic	-0.067	Destabilizing	0.999	D	0.717	prob.delet.	None	None	None	None	N
K/G	0.7474	likely_pathogenic	0.8022	pathogenic	-0.719	Destabilizing	0.993	D	0.577	neutral	None	None	None	None	N
K/H	0.4989	ambiguous	0.5427	ambiguous	-0.913	Destabilizing	0.998	D	0.691	prob.neutral	None	None	None	None	N
K/I	0.369	ambiguous	0.401	ambiguous	0.474	Stabilizing	0.991	D	0.732	prob.delet.	N	0.497293532	None	None	N
K/L	0.3967	ambiguous	0.4234	ambiguous	0.474	Stabilizing	0.986	D	0.577	neutral	None	None	None	None	N
K/M	0.2514	likely_benign	0.2815	benign	0.095	Stabilizing	0.999	D	0.685	prob.neutral	None	None	None	None	N
K/N	0.625	likely_pathogenic	0.6742	pathogenic	-0.291	Destabilizing	0.982	D	0.672	neutral	N	0.518783525	None	None	N
K/P	0.5845	likely_pathogenic	0.6136	pathogenic	0.218	Stabilizing	0.998	D	0.713	prob.delet.	None	None	None	None	N
K/Q	0.1937	likely_benign	0.2136	benign	-0.291	Destabilizing	0.982	D	0.675	prob.neutral	N	0.484689594	None	None	N
K/R	0.1009	likely_benign	0.1131	benign	-0.435	Destabilizing	0.046	N	0.279	neutral	N	0.499755047	None	None	N
K/S	0.6647	likely_pathogenic	0.7025	pathogenic	-0.838	Destabilizing	0.953	D	0.633	neutral	None	None	None	None	N
K/T	0.3068	likely_benign	0.3171	benign	-0.539	Destabilizing	0.991	D	0.643	neutral	N	0.51322299	None	None	N
K/V	0.3673	ambiguous	0.3925	ambiguous	0.218	Stabilizing	0.993	D	0.697	prob.neutral	None	None	None	None	N
K/W	0.8505	likely_pathogenic	0.8933	pathogenic	-0.025	Destabilizing	0.999	D	0.738	prob.delet.	None	None	None	None	N
K/Y	0.7569	likely_pathogenic	0.8075	pathogenic	0.25	Stabilizing	0.998	D	0.701	prob.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.