TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17840	53743;53744;53745	chr2:178607084;178607083;178607082	chr2:179471811;179471810;179471809
N2AB	16199	48820;48821;48822	chr2:178607084;178607083;178607082	chr2:179471811;179471810;179471809
N2A	15272	46039;46040;46041	chr2:178607084;178607083;178607082	chr2:179471811;179471810;179471809
N2B	8775	26548;26549;26550	chr2:178607084;178607083;178607082	chr2:179471811;179471810;179471809
Novex-1	8900	26923;26924;26925	chr2:178607084;178607083;178607082	chr2:179471811;179471810;179471809
Novex-2	8967	27124;27125;27126	chr2:178607084;178607083;178607082	chr2:179471811;179471810;179471809
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: Fn3-17
• Domain position: 77
• Structural Position: 111
• Q(SASA): 0.4437
• Predicted PPI site: I

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	rs769761717	-0.983	0.999	N	0.63	0.295	0.266385636622	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
K/N	rs769761717	-0.983	0.999	N	0.63	0.295	0.266385636622	gnomAD-4.0.0	6.84859E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.9996E-07	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	0.8587	likely_pathogenic	0.7585	pathogenic	-0.988	Destabilizing	0.998	D	0.563	neutral	None	None	None	None	I
K/C	0.7651	likely_pathogenic	0.7511	pathogenic	-1.358	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	I
K/D	0.9829	likely_pathogenic	0.9674	pathogenic	-1.257	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	I
K/E	0.5554	ambiguous	0.3967	ambiguous	-1.079	Destabilizing	0.996	D	0.433	neutral	N	0.382780656	None	None	I
K/F	0.9703	likely_pathogenic	0.9574	pathogenic	-0.618	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	I
K/G	0.943	likely_pathogenic	0.8962	pathogenic	-1.399	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	I
K/H	0.7034	likely_pathogenic	0.6546	pathogenic	-1.737	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	I
K/I	0.7465	likely_pathogenic	0.614	pathogenic	0.116	Stabilizing	1.0	D	0.814	deleterious	None	None	None	None	I
K/L	0.8269	likely_pathogenic	0.7321	pathogenic	0.116	Stabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	I
K/M	0.5928	likely_pathogenic	0.4559	ambiguous	-0.057	Destabilizing	1.0	D	0.729	prob.delet.	N	0.49131363	None	None	I
K/N	0.9386	likely_pathogenic	0.8735	pathogenic	-1.331	Destabilizing	0.999	D	0.63	neutral	N	0.491486989	None	None	I
K/P	0.9963	likely_pathogenic	0.9947	pathogenic	-0.224	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	I
K/Q	0.2731	likely_benign	0.2074	benign	-1.308	Destabilizing	0.999	D	0.626	neutral	N	0.466569901	None	None	I
K/R	0.0915	likely_benign	0.0887	benign	-1.03	Destabilizing	0.884	D	0.311	neutral	N	0.432033253	None	None	I
K/S	0.9005	likely_pathogenic	0.8149	pathogenic	-1.918	Destabilizing	0.998	D	0.513	neutral	None	None	None	None	I
K/T	0.5583	ambiguous	0.391	ambiguous	-1.513	Destabilizing	0.999	D	0.743	deleterious	N	0.481635354	None	None	I
K/V	0.6007	likely_pathogenic	0.4838	ambiguous	-0.224	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	I
K/W	0.9395	likely_pathogenic	0.9313	pathogenic	-0.585	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	I
K/Y	0.9137	likely_pathogenic	0.8834	pathogenic	-0.205	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	I

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.