TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33047	99364;99365;99366	chr2:178538690;178538689;178538688	chr2:179403417;179403416;179403415
N2AB	31406	94441;94442;94443	chr2:178538690;178538689;178538688	chr2:179403417;179403416;179403415
N2A	30479	91660;91661;91662	chr2:178538690;178538689;178538688	chr2:179403417;179403416;179403415
N2B	23982	72169;72170;72171	chr2:178538690;178538689;178538688	chr2:179403417;179403416;179403415
Novex-1	24107	72544;72545;72546	chr2:178538690;178538689;178538688	chr2:179403417;179403416;179403415
Novex-2	24174	72745;72746;72747	chr2:178538690;178538689;178538688	chr2:179403417;179403416;179403415
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: Fn3-129
• Domain position: 50
• Structural Position: 67
• Q(SASA): 0.1982
• 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	None	None	0.999	N	0.591	0.372	0.277730125212	gnomAD-4.0.0	1.59131E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02389E-05
K/N	None	None	1.0	N	0.739	0.301	0.270447802918	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	0.7798	likely_pathogenic	0.7925	pathogenic	-0.571	Destabilizing	0.999	D	0.674	neutral	None	None	None	None	N
K/C	0.9198	likely_pathogenic	0.925	pathogenic	-0.538	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
K/D	0.9383	likely_pathogenic	0.9459	pathogenic	0.185	Stabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
K/E	0.6991	likely_pathogenic	0.6828	pathogenic	0.285	Stabilizing	0.999	D	0.591	neutral	N	0.438495079	None	None	N
K/F	0.9468	likely_pathogenic	0.9453	pathogenic	-0.324	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
K/G	0.8712	likely_pathogenic	0.8932	pathogenic	-0.913	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
K/H	0.674	likely_pathogenic	0.6805	pathogenic	-1.173	Destabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
K/I	0.6667	likely_pathogenic	0.6451	pathogenic	0.301	Stabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
K/L	0.6655	likely_pathogenic	0.6568	pathogenic	0.301	Stabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
K/M	0.5513	ambiguous	0.5458	ambiguous	0.147	Stabilizing	1.0	D	0.754	deleterious	N	0.489678834	None	None	N
K/N	0.825	likely_pathogenic	0.85	pathogenic	-0.244	Destabilizing	1.0	D	0.739	prob.delet.	N	0.486483814	None	None	N
K/P	0.7905	likely_pathogenic	0.8073	pathogenic	0.04	Stabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
K/Q	0.3658	ambiguous	0.3522	ambiguous	-0.321	Destabilizing	1.0	D	0.712	prob.delet.	N	0.474285307	None	None	N
K/R	0.1162	likely_benign	0.1088	benign	-0.416	Destabilizing	0.999	D	0.516	neutral	N	0.388629193	None	None	N
K/S	0.8747	likely_pathogenic	0.8953	pathogenic	-0.956	Destabilizing	0.999	D	0.656	neutral	None	None	None	None	N
K/T	0.604	likely_pathogenic	0.6149	pathogenic	-0.647	Destabilizing	1.0	D	0.771	deleterious	N	0.457160984	None	None	N
K/V	0.6551	likely_pathogenic	0.6385	pathogenic	0.04	Stabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
K/W	0.9513	likely_pathogenic	0.9502	pathogenic	-0.175	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
K/Y	0.8771	likely_pathogenic	0.8818	pathogenic	0.104	Stabilizing	1.0	D	0.785	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.