TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32734	98425;98426;98427	chr2:178539865;178539864;178539863	chr2:179404592;179404591;179404590
N2AB	31093	93502;93503;93504	chr2:178539865;178539864;178539863	chr2:179404592;179404591;179404590
N2A	30166	90721;90722;90723	chr2:178539865;178539864;178539863	chr2:179404592;179404591;179404590
N2B	23669	71230;71231;71232	chr2:178539865;178539864;178539863	chr2:179404592;179404591;179404590
Novex-1	23794	71605;71606;71607	chr2:178539865;178539864;178539863	chr2:179404592;179404591;179404590
Novex-2	23861	71806;71807;71808	chr2:178539865;178539864;178539863	chr2:179404592;179404591;179404590
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-155
• Domain position: 27
• Structural Position: 44
• Q(SASA): 0.1363
• 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
P/Q	rs1559091870	None	0.999	D	0.79	0.553	0.633466640759	gnomAD-4.0.0	2.40067E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.62503E-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
P/A	0.8909	likely_pathogenic	0.8495	pathogenic	-1.409	Destabilizing	0.984	D	0.599	neutral	D	0.527650009	None	None	I
P/C	0.9868	likely_pathogenic	0.9787	pathogenic	-0.996	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	I
P/D	0.9992	likely_pathogenic	0.9989	pathogenic	-0.858	Destabilizing	0.998	D	0.775	deleterious	None	None	None	None	I
P/E	0.9981	likely_pathogenic	0.9975	pathogenic	-0.851	Destabilizing	0.998	D	0.773	deleterious	None	None	None	None	I
P/F	0.9987	likely_pathogenic	0.998	pathogenic	-1.078	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	I
P/G	0.9913	likely_pathogenic	0.9885	pathogenic	-1.732	Destabilizing	0.994	D	0.704	prob.neutral	None	None	None	None	I
P/H	0.9956	likely_pathogenic	0.9943	pathogenic	-1.293	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	I
P/I	0.9854	likely_pathogenic	0.9787	pathogenic	-0.623	Destabilizing	0.999	D	0.778	deleterious	None	None	None	None	I
P/K	0.9987	likely_pathogenic	0.9982	pathogenic	-1.032	Destabilizing	0.998	D	0.77	deleterious	None	None	None	None	I
P/L	0.9448	likely_pathogenic	0.9288	pathogenic	-0.623	Destabilizing	0.998	D	0.752	deleterious	D	0.5537263	None	None	I
P/M	0.9945	likely_pathogenic	0.9918	pathogenic	-0.528	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	I
P/N	0.9987	likely_pathogenic	0.9982	pathogenic	-0.807	Destabilizing	0.998	D	0.758	deleterious	None	None	None	None	I
P/Q	0.9945	likely_pathogenic	0.9929	pathogenic	-0.948	Destabilizing	0.999	D	0.79	deleterious	D	0.558289112	None	None	I
P/R	0.9935	likely_pathogenic	0.9914	pathogenic	-0.623	Destabilizing	0.999	D	0.771	deleterious	D	0.558289112	None	None	I
P/S	0.984	likely_pathogenic	0.9782	pathogenic	-1.411	Destabilizing	0.79	D	0.452	neutral	D	0.546261243	None	None	I
P/T	0.9791	likely_pathogenic	0.9714	pathogenic	-1.287	Destabilizing	0.995	D	0.761	deleterious	D	0.557782132	None	None	I
P/V	0.9651	likely_pathogenic	0.9499	pathogenic	-0.85	Destabilizing	0.998	D	0.751	deleterious	None	None	None	None	I
P/W	0.9996	likely_pathogenic	0.9994	pathogenic	-1.242	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	I
P/Y	0.9991	likely_pathogenic	0.9986	pathogenic	-0.938	Destabilizing	1.0	D	0.779	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.