TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27793	83602;83603;83604	chr2:178562755;178562754;178562753	chr2:179427482;179427481;179427480
N2AB	26152	78679;78680;78681	chr2:178562755;178562754;178562753	chr2:179427482;179427481;179427480
N2A	25225	75898;75899;75900	chr2:178562755;178562754;178562753	chr2:179427482;179427481;179427480
N2B	18728	56407;56408;56409	chr2:178562755;178562754;178562753	chr2:179427482;179427481;179427480
Novex-1	18853	56782;56783;56784	chr2:178562755;178562754;178562753	chr2:179427482;179427481;179427480
Novex-2	18920	56983;56984;56985	chr2:178562755;178562754;178562753	chr2:179427482;179427481;179427480
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-90
• Domain position: 28
• Structural Position: 30
• Q(SASA): 0.3072
• 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
D/G	None	None	0.753	N	0.587	0.466	0.367042808489	gnomAD-4.0.0	1.594E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86256E-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
D/A	0.9529	likely_pathogenic	0.9503	pathogenic	-0.486	Destabilizing	0.967	D	0.615	neutral	N	0.496020406	None	None	I
D/C	0.9922	likely_pathogenic	0.9915	pathogenic	-0.025	Destabilizing	0.996	D	0.657	neutral	None	None	None	None	I
D/E	0.9029	likely_pathogenic	0.8803	pathogenic	-0.695	Destabilizing	0.486	N	0.433	neutral	N	0.488258499	None	None	I
D/F	0.9946	likely_pathogenic	0.9937	pathogenic	-0.52	Destabilizing	1.0	D	0.66	neutral	None	None	None	None	I
D/G	0.9423	likely_pathogenic	0.9414	pathogenic	-0.769	Destabilizing	0.753	D	0.587	neutral	N	0.513670589	None	None	I
D/H	0.9706	likely_pathogenic	0.9696	pathogenic	-0.838	Destabilizing	0.997	D	0.691	prob.neutral	N	0.51965807	None	None	I
D/I	0.9901	likely_pathogenic	0.9879	pathogenic	0.238	Stabilizing	0.996	D	0.669	neutral	None	None	None	None	I
D/K	0.9916	likely_pathogenic	0.9907	pathogenic	-0.095	Destabilizing	0.993	D	0.626	neutral	None	None	None	None	I
D/L	0.985	likely_pathogenic	0.9827	pathogenic	0.238	Stabilizing	0.996	D	0.653	neutral	None	None	None	None	I
D/M	0.9958	likely_pathogenic	0.9952	pathogenic	0.688	Stabilizing	0.999	D	0.647	neutral	None	None	None	None	I
D/N	0.4928	ambiguous	0.5137	ambiguous	-0.413	Destabilizing	0.026	N	0.266	neutral	D	0.526004994	None	None	I
D/P	0.9928	likely_pathogenic	0.9931	pathogenic	0.021	Stabilizing	0.945	D	0.713	prob.delet.	None	None	None	None	I
D/Q	0.9839	likely_pathogenic	0.983	pathogenic	-0.343	Destabilizing	0.981	D	0.728	prob.delet.	None	None	None	None	I
D/R	0.988	likely_pathogenic	0.9867	pathogenic	-0.093	Destabilizing	0.993	D	0.686	prob.neutral	None	None	None	None	I
D/S	0.7735	likely_pathogenic	0.7796	pathogenic	-0.599	Destabilizing	0.848	D	0.585	neutral	None	None	None	None	I
D/T	0.9267	likely_pathogenic	0.9283	pathogenic	-0.372	Destabilizing	0.946	D	0.62	neutral	None	None	None	None	I
D/V	0.9758	likely_pathogenic	0.9696	pathogenic	0.021	Stabilizing	0.974	D	0.654	neutral	N	0.512403141	None	None	I
D/W	0.9986	likely_pathogenic	0.9986	pathogenic	-0.435	Destabilizing	1.0	D	0.669	neutral	None	None	None	None	I
D/Y	0.9573	likely_pathogenic	0.9532	pathogenic	-0.293	Destabilizing	1.0	D	0.655	neutral	D	0.549879099	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.