TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7014	21265;21266;21267	chr2:178724335;178724334;178724333	chr2:179589062;179589061;179589060
N2AB	6697	20314;20315;20316	chr2:178724335;178724334;178724333	chr2:179589062;179589061;179589060
N2A	5770	17533;17534;17535	chr2:178724335;178724334;178724333	chr2:179589062;179589061;179589060
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: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-54
• Domain position: 67
• Structural Position: 149
• Q(SASA): 0.1506
• 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/N	rs1256056605	None	0.993	D	0.789	0.639	0.664611728801	gnomAD-4.0.0	1.36862E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	1.73611E-04	8.99564E-07	0	0
D/V	rs1484212258	None	0.997	D	0.874	0.839	0.922917791787	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
D/V	rs1484212258	None	0.997	D	0.874	0.839	0.922917791787	gnomAD-4.0.0	6.57125E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47029E-05	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	0.8821	likely_pathogenic	0.8062	pathogenic	0.197	Stabilizing	0.993	D	0.823	deleterious	D	0.609047792	None	None	N
D/C	0.974	likely_pathogenic	0.9516	pathogenic	0.007	Stabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
D/E	0.7886	likely_pathogenic	0.6853	pathogenic	-0.939	Destabilizing	0.117	N	0.345	neutral	D	0.596925228	None	None	N
D/F	0.9742	likely_pathogenic	0.9578	pathogenic	0.741	Stabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
D/G	0.8808	likely_pathogenic	0.8197	pathogenic	-0.271	Destabilizing	0.977	D	0.769	deleterious	D	0.630608744	None	None	N
D/H	0.8544	likely_pathogenic	0.7677	pathogenic	0.167	Stabilizing	0.999	D	0.825	deleterious	D	0.575091032	None	None	N
D/I	0.9699	likely_pathogenic	0.9468	pathogenic	1.46	Stabilizing	0.998	D	0.872	deleterious	None	None	None	None	N
D/K	0.9779	likely_pathogenic	0.965	pathogenic	-0.571	Destabilizing	0.99	D	0.803	deleterious	None	None	None	None	N
D/L	0.9674	likely_pathogenic	0.9497	pathogenic	1.46	Stabilizing	0.995	D	0.873	deleterious	None	None	None	None	N
D/M	0.9764	likely_pathogenic	0.9592	pathogenic	1.917	Stabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
D/N	0.6969	likely_pathogenic	0.5458	ambiguous	-1.173	Destabilizing	0.993	D	0.789	deleterious	D	0.58909235	None	None	N
D/P	0.9954	likely_pathogenic	0.994	pathogenic	1.068	Stabilizing	0.998	D	0.824	deleterious	None	None	None	None	N
D/Q	0.9354	likely_pathogenic	0.8932	pathogenic	-0.797	Destabilizing	0.99	D	0.795	deleterious	None	None	None	None	N
D/R	0.9821	likely_pathogenic	0.9733	pathogenic	-0.557	Destabilizing	0.995	D	0.86	deleterious	None	None	None	None	N
D/S	0.8137	likely_pathogenic	0.692	pathogenic	-1.492	Destabilizing	0.983	D	0.693	prob.neutral	None	None	None	None	N
D/T	0.9426	likely_pathogenic	0.8961	pathogenic	-1.082	Destabilizing	0.995	D	0.819	deleterious	None	None	None	None	N
D/V	0.9118	likely_pathogenic	0.8605	pathogenic	1.068	Stabilizing	0.997	D	0.874	deleterious	D	0.647031714	None	None	N
D/W	0.9935	likely_pathogenic	0.9905	pathogenic	0.616	Stabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
D/Y	0.8333	likely_pathogenic	0.7606	pathogenic	0.898	Stabilizing	1.0	D	0.881	deleterious	D	0.630810549	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.