TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18156	54691;54692;54693	chr2:178604221;178604220;178604219	chr2:179468948;179468947;179468946
N2AB	16515	49768;49769;49770	chr2:178604221;178604220;178604219	chr2:179468948;179468947;179468946
N2A	15588	46987;46988;46989	chr2:178604221;178604220;178604219	chr2:179468948;179468947;179468946
N2B	9091	27496;27497;27498	chr2:178604221;178604220;178604219	chr2:179468948;179468947;179468946
Novex-1	9216	27871;27872;27873	chr2:178604221;178604220;178604219	chr2:179468948;179468947;179468946
Novex-2	9283	28072;28073;28074	chr2:178604221;178604220;178604219	chr2:179468948;179468947;179468946
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: Fn3-19
• Domain position: 92
• Structural Position: 125
• Q(SASA): 0.8868
• 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
D/H	None	None	0.895	N	0.566	0.292	0.289474373501	gnomAD-4.0.0	1.6119E-06	None	None	None	None	N	None	0	2.32245E-05	None	0	0	None	0	0	0	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	0.128	likely_benign	0.107	benign	0.01	Stabilizing	0.376	N	0.545	neutral	N	0.443055536	None	None	N
D/C	0.6056	likely_pathogenic	0.5016	ambiguous	0.13	Stabilizing	0.992	D	0.759	deleterious	None	None	None	None	N
D/E	0.078	likely_benign	0.0758	benign	-0.167	Destabilizing	0.002	N	0.146	neutral	N	0.356724631	None	None	N
D/F	0.6434	likely_pathogenic	0.5281	ambiguous	-0.04	Destabilizing	0.972	D	0.73	deleterious	None	None	None	None	N
D/G	0.1285	likely_benign	0.1053	benign	-0.146	Destabilizing	0.004	N	0.421	neutral	N	0.460507934	None	None	N
D/H	0.2886	likely_benign	0.2218	benign	0.269	Stabilizing	0.895	D	0.566	neutral	N	0.504048067	None	None	N
D/I	0.3518	ambiguous	0.2632	benign	0.354	Stabilizing	0.919	D	0.734	deleterious	None	None	None	None	N
D/K	0.2062	likely_benign	0.1785	benign	0.548	Stabilizing	0.444	N	0.453	neutral	None	None	None	None	N
D/L	0.3396	likely_benign	0.2642	benign	0.354	Stabilizing	0.848	D	0.672	prob.neutral	None	None	None	None	N
D/M	0.5082	ambiguous	0.433	ambiguous	0.325	Stabilizing	0.992	D	0.721	deleterious	None	None	None	None	N
D/N	0.098	likely_benign	0.0804	benign	0.323	Stabilizing	0.546	D	0.594	neutral	N	0.447501351	None	None	N
D/P	0.3267	likely_benign	0.3056	benign	0.261	Stabilizing	0.919	D	0.603	neutral	None	None	None	None	N
D/Q	0.1899	likely_benign	0.1669	benign	0.339	Stabilizing	0.737	D	0.524	neutral	None	None	None	None	N
D/R	0.2804	likely_benign	0.2395	benign	0.68	Stabilizing	0.848	D	0.723	deleterious	None	None	None	None	N
D/S	0.1034	likely_benign	0.0872	benign	0.221	Stabilizing	0.444	N	0.463	neutral	None	None	None	None	N
D/T	0.1861	likely_benign	0.1522	benign	0.343	Stabilizing	0.615	D	0.579	neutral	None	None	None	None	N
D/V	0.2083	likely_benign	0.1559	benign	0.261	Stabilizing	0.808	D	0.625	neutral	N	0.430531743	None	None	N
D/W	0.8602	likely_pathogenic	0.8198	pathogenic	0.022	Stabilizing	0.992	D	0.773	deleterious	None	None	None	None	N
D/Y	0.317	likely_benign	0.2413	benign	0.194	Stabilizing	0.963	D	0.73	deleterious	N	0.504221425	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.