TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34942	105049;105050;105051	chr2:178531791;178531790;178531789	chr2:179396518;179396517;179396516
N2AB	33301	100126;100127;100128	chr2:178531791;178531790;178531789	chr2:179396518;179396517;179396516
N2A	32374	97345;97346;97347	chr2:178531791;178531790;178531789	chr2:179396518;179396517;179396516
N2B	25877	77854;77855;77856	chr2:178531791;178531790;178531789	chr2:179396518;179396517;179396516
Novex-1	26002	78229;78230;78231	chr2:178531791;178531790;178531789	chr2:179396518;179396517;179396516
Novex-2	26069	78430;78431;78432	chr2:178531791;178531790;178531789	chr2:179396518;179396517;179396516
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-163
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.1338
• 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
P/T	None	None	1.0	D	0.908	0.801	0.707650254962	gnomAD-4.0.0	1.59089E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43271E-05	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
P/A	0.89	likely_pathogenic	0.9296	pathogenic	-1.5	Destabilizing	1.0	D	0.827	deleterious	D	0.617244994	None	None	N
P/C	0.9963	likely_pathogenic	0.9976	pathogenic	-1.328	Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
P/D	0.9994	likely_pathogenic	0.9995	pathogenic	-2.014	Highly Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	N
P/E	0.9985	likely_pathogenic	0.9986	pathogenic	-2.046	Highly Destabilizing	1.0	D	0.909	deleterious	None	None	None	None	N
P/F	0.9998	likely_pathogenic	0.9998	pathogenic	-1.472	Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
P/G	0.9925	likely_pathogenic	0.9951	pathogenic	-1.762	Destabilizing	1.0	D	0.9	deleterious	None	None	None	None	N
P/H	0.9989	likely_pathogenic	0.9988	pathogenic	-1.256	Destabilizing	1.0	D	0.871	deleterious	D	0.617850407	None	None	N
P/I	0.9974	likely_pathogenic	0.9978	pathogenic	-0.885	Destabilizing	1.0	D	0.896	deleterious	None	None	None	None	N
P/K	0.9993	likely_pathogenic	0.9993	pathogenic	-1.187	Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
P/L	0.9864	likely_pathogenic	0.9857	pathogenic	-0.885	Destabilizing	1.0	D	0.903	deleterious	D	0.617648603	None	None	N
P/M	0.9985	likely_pathogenic	0.9987	pathogenic	-0.706	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
P/N	0.999	likely_pathogenic	0.9991	pathogenic	-1.092	Destabilizing	1.0	D	0.906	deleterious	None	None	None	None	N
P/Q	0.9976	likely_pathogenic	0.9976	pathogenic	-1.386	Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
P/R	0.9975	likely_pathogenic	0.9972	pathogenic	-0.612	Destabilizing	1.0	D	0.909	deleterious	D	0.617850407	None	None	N
P/S	0.9846	likely_pathogenic	0.9876	pathogenic	-1.521	Destabilizing	1.0	D	0.907	deleterious	D	0.580068289	None	None	N
P/T	0.9882	likely_pathogenic	0.9902	pathogenic	-1.455	Destabilizing	1.0	D	0.908	deleterious	D	0.617648603	None	None	N
P/V	0.988	likely_pathogenic	0.9903	pathogenic	-1.058	Destabilizing	1.0	D	0.909	deleterious	None	None	None	None	N
P/W	0.9999	likely_pathogenic	0.9999	pathogenic	-1.607	Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
P/Y	0.9998	likely_pathogenic	0.9998	pathogenic	-1.291	Destabilizing	1.0	D	0.909	deleterious	None	None	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.