TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7099	21520;21521;21522	chr2:178723964;178723963;178723962	chr2:179588691;179588690;179588689
N2AB	6782	20569;20570;20571	chr2:178723964;178723963;178723962	chr2:179588691;179588690;179588689
N2A	5855	17788;17789;17790	chr2:178723964;178723963;178723962	chr2:179588691;179588690;179588689
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: C
• RefSeq wild type transcript codon: TGC
• RefSeq wild type template codon: ACG
• Domain: Ig-55
• Domain position: 56
• Structural Position: 136
• Q(SASA): 0.1176
• 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
C/Y	rs2078895939	None	0.238	N	0.638	0.199	0.485420873983	gnomAD-4.0.0	3.42161E-06	None	None	None	None	N	None	0	0	None	0	2.52003E-05	None	0	0	3.59838E-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
C/A	0.6124	likely_pathogenic	0.6214	pathogenic	-1.794	Destabilizing	0.055	N	0.335	neutral	None	None	None	None	N
C/D	0.9883	likely_pathogenic	0.9919	pathogenic	-1.433	Destabilizing	0.995	D	0.806	deleterious	None	None	None	None	N
C/E	0.9928	likely_pathogenic	0.995	pathogenic	-1.203	Destabilizing	0.984	D	0.795	deleterious	None	None	None	None	N
C/F	0.564	ambiguous	0.6151	pathogenic	-1.185	Destabilizing	0.921	D	0.777	deleterious	N	0.478970475	None	None	N
C/G	0.4639	ambiguous	0.4956	ambiguous	-2.16	Highly Destabilizing	0.906	D	0.733	prob.delet.	N	0.469983061	None	None	N
C/H	0.9397	likely_pathogenic	0.9468	pathogenic	-2.355	Highly Destabilizing	0.995	D	0.784	deleterious	None	None	None	None	N
C/I	0.745	likely_pathogenic	0.8224	pathogenic	-0.801	Destabilizing	0.984	D	0.755	deleterious	None	None	None	None	N
C/K	0.9934	likely_pathogenic	0.9957	pathogenic	-1.11	Destabilizing	0.984	D	0.791	deleterious	None	None	None	None	N
C/L	0.7057	likely_pathogenic	0.7419	pathogenic	-0.801	Destabilizing	0.927	D	0.701	prob.neutral	None	None	None	None	N
C/M	0.8491	likely_pathogenic	0.8875	pathogenic	0.202	Stabilizing	0.999	D	0.759	deleterious	None	None	None	None	N
C/N	0.9435	likely_pathogenic	0.956	pathogenic	-1.689	Destabilizing	0.999	D	0.809	deleterious	None	None	None	None	N
C/P	0.9917	likely_pathogenic	0.9946	pathogenic	-1.109	Destabilizing	0.995	D	0.811	deleterious	None	None	None	None	N
C/Q	0.9702	likely_pathogenic	0.975	pathogenic	-1.246	Destabilizing	0.999	D	0.811	deleterious	None	None	None	None	N
C/R	0.9441	likely_pathogenic	0.9567	pathogenic	-1.486	Destabilizing	0.994	D	0.812	deleterious	N	0.451840546	None	None	N
C/S	0.6195	likely_pathogenic	0.6284	pathogenic	-2.03	Highly Destabilizing	0.828	D	0.699	prob.neutral	N	0.464305095	None	None	N
C/T	0.7884	likely_pathogenic	0.8417	pathogenic	-1.607	Destabilizing	0.969	D	0.733	prob.delet.	None	None	None	None	N
C/V	0.6405	likely_pathogenic	0.716	pathogenic	-1.109	Destabilizing	0.927	D	0.709	prob.delet.	None	None	None	None	N
C/W	0.906	likely_pathogenic	0.9229	pathogenic	-1.523	Destabilizing	0.999	D	0.744	deleterious	N	0.480998391	None	None	N
C/Y	0.7772	likely_pathogenic	0.787	pathogenic	-1.353	Destabilizing	0.238	N	0.638	neutral	N	0.450016894	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.