TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7162	21709;21710;21711	chr2:178723616;178723615;178723614	chr2:179588343;179588342;179588341
N2AB	6845	20758;20759;20760	chr2:178723616;178723615;178723614	chr2:179588343;179588342;179588341
N2A	5918	17977;17978;17979	chr2:178723616;178723615;178723614	chr2:179588343;179588342;179588341
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: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Ig-56
• Domain position: 26
• Structural Position: 40
• Q(SASA): 0.3038
• 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
G/R	rs1288993592	-0.487	1.0	D	0.805	0.642	0.883724802589	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.94E-06	0
G/R	rs1288993592	-0.487	1.0	D	0.805	0.642	0.883724802589	gnomAD-4.0.0	1.59343E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86084E-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
G/A	0.7381	likely_pathogenic	0.6869	pathogenic	-0.296	Destabilizing	1.0	D	0.771	deleterious	D	0.567876081	None	None	I
G/C	0.9546	likely_pathogenic	0.9446	pathogenic	-0.844	Destabilizing	1.0	D	0.704	prob.neutral	None	None	None	None	I
G/D	0.9796	likely_pathogenic	0.9756	pathogenic	-0.573	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	I
G/E	0.9843	likely_pathogenic	0.9827	pathogenic	-0.678	Destabilizing	1.0	D	0.813	deleterious	D	0.609504993	None	None	I
G/F	0.994	likely_pathogenic	0.9925	pathogenic	-0.813	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	I
G/H	0.9966	likely_pathogenic	0.9957	pathogenic	-0.63	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	I
G/I	0.9836	likely_pathogenic	0.9802	pathogenic	-0.219	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	I
G/K	0.9958	likely_pathogenic	0.9953	pathogenic	-0.934	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	I
G/L	0.9889	likely_pathogenic	0.9867	pathogenic	-0.219	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	I
G/M	0.9919	likely_pathogenic	0.9905	pathogenic	-0.473	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	I
G/N	0.988	likely_pathogenic	0.9861	pathogenic	-0.626	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	I
G/P	0.9976	likely_pathogenic	0.9971	pathogenic	-0.208	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	I
G/Q	0.9933	likely_pathogenic	0.9923	pathogenic	-0.808	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	I
G/R	0.9895	likely_pathogenic	0.988	pathogenic	-0.581	Destabilizing	1.0	D	0.805	deleterious	D	0.638443416	None	None	I
G/S	0.7992	likely_pathogenic	0.7577	pathogenic	-0.799	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	I
G/T	0.9615	likely_pathogenic	0.954	pathogenic	-0.819	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	I
G/V	0.9598	likely_pathogenic	0.9521	pathogenic	-0.208	Destabilizing	1.0	D	0.783	deleterious	D	0.62915683	None	None	I
G/W	0.9872	likely_pathogenic	0.985	pathogenic	-1.076	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	I
G/Y	0.9918	likely_pathogenic	0.9901	pathogenic	-0.676	Destabilizing	1.0	D	0.741	deleterious	None	None	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.