TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5947	18064;18065;18066	chr2:178730694;178730693;178730692	chr2:179595421;179595420;179595419
N2AB	5630	17113;17114;17115	chr2:178730694;178730693;178730692	chr2:179595421;179595420;179595419
N2A	4703	14332;14333;14334	chr2:178730694;178730693;178730692	chr2:179595421;179595420;179595419
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: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Ig-43
• Domain position: 29
• Structural Position: 43
• Q(SASA): 0.7418
• 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/A	None	None	1.0	N	0.655	0.513	0.457922657367	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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	0.8199	likely_pathogenic	0.8992	pathogenic	-0.427	Destabilizing	1.0	D	0.655	neutral	N	0.490946249	None	None	I
P/C	0.9932	likely_pathogenic	0.9964	pathogenic	-0.436	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	I
P/D	0.9546	likely_pathogenic	0.9765	pathogenic	-0.445	Destabilizing	1.0	D	0.669	neutral	None	None	None	None	I
P/E	0.9403	likely_pathogenic	0.9732	pathogenic	-0.561	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	I
P/F	0.9933	likely_pathogenic	0.9971	pathogenic	-0.72	Destabilizing	1.0	D	0.641	neutral	None	None	None	None	I
P/G	0.9479	likely_pathogenic	0.969	pathogenic	-0.555	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	I
P/H	0.9459	likely_pathogenic	0.9721	pathogenic	-0.21	Destabilizing	1.0	D	0.647	neutral	D	0.527941681	None	None	I
P/I	0.9717	likely_pathogenic	0.9857	pathogenic	-0.236	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	I
P/K	0.9689	likely_pathogenic	0.9849	pathogenic	-0.417	Destabilizing	1.0	D	0.67	neutral	None	None	None	None	I
P/L	0.9033	likely_pathogenic	0.9513	pathogenic	-0.236	Destabilizing	1.0	D	0.702	prob.neutral	N	0.48570601	None	None	I
P/M	0.9752	likely_pathogenic	0.9874	pathogenic	-0.308	Destabilizing	1.0	D	0.65	neutral	None	None	None	None	I
P/N	0.9534	likely_pathogenic	0.9752	pathogenic	-0.051	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	I
P/Q	0.9182	likely_pathogenic	0.9608	pathogenic	-0.308	Destabilizing	1.0	D	0.653	neutral	None	None	None	None	I
P/R	0.9259	likely_pathogenic	0.9629	pathogenic	0.088	Stabilizing	1.0	D	0.685	prob.neutral	N	0.487681019	None	None	I
P/S	0.9166	likely_pathogenic	0.9581	pathogenic	-0.355	Destabilizing	1.0	D	0.691	prob.neutral	N	0.49498517399999997	None	None	I
P/T	0.863	likely_pathogenic	0.9271	pathogenic	-0.376	Destabilizing	1.0	D	0.684	prob.neutral	N	0.482285742	None	None	I
P/V	0.9426	likely_pathogenic	0.9688	pathogenic	-0.266	Destabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	I
P/W	0.9966	likely_pathogenic	0.9984	pathogenic	-0.818	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	I
P/Y	0.9894	likely_pathogenic	0.9951	pathogenic	-0.511	Destabilizing	1.0	D	0.649	neutral	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.