TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2735	8428;8429;8430	chr2:178770589;178770588;178770587	chr2:179635316;179635315;179635314
N2AB	2735	8428;8429;8430	chr2:178770589;178770588;178770587	chr2:179635316;179635315;179635314
N2A	2735	8428;8429;8430	chr2:178770589;178770588;178770587	chr2:179635316;179635315;179635314
N2B	2689	8290;8291;8292	chr2:178770589;178770588;178770587	chr2:179635316;179635315;179635314
Novex-1	2689	8290;8291;8292	chr2:178770589;178770588;178770587	chr2:179635316;179635315;179635314
Novex-2	2689	8290;8291;8292	chr2:178770589;178770588;178770587	chr2:179635316;179635315;179635314
Novex-3	2735	8428;8429;8430	chr2:178770589;178770588;178770587	chr2:179635316;179635315;179635314

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-17
• Domain position: 29
• Structural Position: 43
• Q(SASA): 0.1483
• 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
V/A	rs1352413380	-1.445	0.958	N	0.554	0.327	0.662113396273	gnomAD-2.1.1	3.98E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.8E-06	0
V/A	rs1352413380	-1.445	0.958	N	0.554	0.327	0.662113396273	gnomAD-4.0.0	3.42038E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.49648E-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
V/A	0.475	ambiguous	0.5706	pathogenic	-1.408	Destabilizing	0.958	D	0.554	neutral	N	0.507081171	None	None	N
V/C	0.8906	likely_pathogenic	0.9211	pathogenic	-1.089	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
V/D	0.8207	likely_pathogenic	0.8918	pathogenic	-1.198	Destabilizing	0.998	D	0.775	deleterious	D	0.656831713	None	None	N
V/E	0.6719	likely_pathogenic	0.7712	pathogenic	-1.118	Destabilizing	0.998	D	0.735	prob.delet.	None	None	None	None	N
V/F	0.4239	ambiguous	0.4858	ambiguous	-0.969	Destabilizing	0.988	D	0.756	deleterious	D	0.664228712	None	None	N
V/G	0.5655	likely_pathogenic	0.6679	pathogenic	-1.737	Destabilizing	0.994	D	0.749	deleterious	D	0.600339193	None	None	N
V/H	0.9131	likely_pathogenic	0.9432	pathogenic	-0.984	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
V/I	0.1042	likely_benign	0.1092	benign	-0.567	Destabilizing	0.067	N	0.308	neutral	N	0.509555358	None	None	N
V/K	0.7887	likely_pathogenic	0.856	pathogenic	-1.076	Destabilizing	0.995	D	0.742	deleterious	None	None	None	None	N
V/L	0.4353	ambiguous	0.4737	ambiguous	-0.567	Destabilizing	0.618	D	0.517	neutral	D	0.598670852	None	None	N
V/M	0.2714	likely_benign	0.2957	benign	-0.748	Destabilizing	0.991	D	0.759	deleterious	None	None	None	None	N
V/N	0.7647	likely_pathogenic	0.8323	pathogenic	-1.125	Destabilizing	0.998	D	0.769	deleterious	None	None	None	None	N
V/P	0.8921	likely_pathogenic	0.9263	pathogenic	-0.818	Destabilizing	0.998	D	0.769	deleterious	None	None	None	None	N
V/Q	0.7184	likely_pathogenic	0.7927	pathogenic	-1.139	Destabilizing	0.998	D	0.763	deleterious	None	None	None	None	N
V/R	0.7457	likely_pathogenic	0.8186	pathogenic	-0.731	Destabilizing	0.998	D	0.767	deleterious	None	None	None	None	N
V/S	0.6278	likely_pathogenic	0.7278	pathogenic	-1.643	Destabilizing	0.995	D	0.748	deleterious	None	None	None	None	N
V/T	0.497	ambiguous	0.5842	pathogenic	-1.43	Destabilizing	0.968	D	0.697	prob.neutral	None	None	None	None	N
V/W	0.9539	likely_pathogenic	0.968	pathogenic	-1.117	Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	N
V/Y	0.8537	likely_pathogenic	0.8998	pathogenic	-0.819	Destabilizing	0.995	D	0.765	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.