TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5377	16354;16355;16356	chr2:178733047;178733046;178733045	chr2:179597774;179597773;179597772
N2AB	5060	15403;15404;15405	chr2:178733047;178733046;178733045	chr2:179597774;179597773;179597772
N2A	4133	12622;12623;12624	chr2:178733047;178733046;178733045	chr2:179597774;179597773;179597772
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-37
• Domain position: 21
• Structural Position: 31
• Q(SASA): 0.2422
• 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/V	None	None	0.997	N	0.765	0.54	0.714182674065	gnomAD-4.0.0	1.59243E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85969E-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	0.3243	likely_benign	0.2961	benign	-0.471	Destabilizing	0.977	D	0.656	neutral	N	0.507891741	None	None	N
D/C	0.8232	likely_pathogenic	0.7915	pathogenic	-0.19	Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
D/E	0.2081	likely_benign	0.1876	benign	-0.758	Destabilizing	0.117	N	0.261	neutral	N	0.409997047	None	None	N
D/F	0.7281	likely_pathogenic	0.6947	pathogenic	None	Stabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
D/G	0.373	ambiguous	0.3373	benign	-0.857	Destabilizing	0.989	D	0.635	neutral	N	0.483263701	None	None	N
D/H	0.4713	ambiguous	0.4192	ambiguous	-0.343	Destabilizing	0.999	D	0.802	deleterious	N	0.495637306	None	None	N
D/I	0.5368	ambiguous	0.4889	ambiguous	0.557	Stabilizing	0.998	D	0.813	deleterious	None	None	None	None	N
D/K	0.7371	likely_pathogenic	0.682	pathogenic	-0.301	Destabilizing	0.99	D	0.701	prob.neutral	None	None	None	None	N
D/L	0.5664	likely_pathogenic	0.5285	ambiguous	0.557	Stabilizing	0.995	D	0.774	deleterious	None	None	None	None	N
D/M	0.7908	likely_pathogenic	0.7598	pathogenic	0.994	Stabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
D/N	0.1969	likely_benign	0.179	benign	-0.832	Destabilizing	0.993	D	0.669	neutral	N	0.491575494	None	None	N
D/P	0.9194	likely_pathogenic	0.927	pathogenic	0.24	Stabilizing	0.998	D	0.773	deleterious	None	None	None	None	N
D/Q	0.5207	ambiguous	0.4721	ambiguous	-0.661	Destabilizing	0.99	D	0.735	prob.delet.	None	None	None	None	N
D/R	0.7056	likely_pathogenic	0.6525	pathogenic	-0.157	Destabilizing	0.995	D	0.757	deleterious	None	None	None	None	N
D/S	0.2339	likely_benign	0.211	benign	-1.107	Destabilizing	0.983	D	0.555	neutral	None	None	None	None	N
D/T	0.4039	ambiguous	0.3671	ambiguous	-0.779	Destabilizing	0.995	D	0.719	prob.delet.	None	None	None	None	N
D/V	0.3346	likely_benign	0.3	benign	0.24	Stabilizing	0.997	D	0.765	deleterious	N	0.48082257	None	None	N
D/W	0.9395	likely_pathogenic	0.9304	pathogenic	0.182	Stabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
D/Y	0.3894	ambiguous	0.344	ambiguous	0.264	Stabilizing	1.0	D	0.819	deleterious	D	0.524362703	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.