TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25327	76204;76205;76206	chr2:178570153;178570152;178570151	chr2:179434880;179434879;179434878
N2AB	23686	71281;71282;71283	chr2:178570153;178570152;178570151	chr2:179434880;179434879;179434878
N2A	22759	68500;68501;68502	chr2:178570153;178570152;178570151	chr2:179434880;179434879;179434878
N2B	16262	49009;49010;49011	chr2:178570153;178570152;178570151	chr2:179434880;179434879;179434878
Novex-1	16387	49384;49385;49386	chr2:178570153;178570152;178570151	chr2:179434880;179434879;179434878
Novex-2	16454	49585;49586;49587	chr2:178570153;178570152;178570151	chr2:179434880;179434879;179434878
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Fn3-72
• Domain position: 24
• Structural Position: 26
• Q(SASA): 0.724
• 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
R/S	None	None	0.805	D	0.615	0.225	0.213573922156	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
R/A	0.5557	ambiguous	0.5824	pathogenic	-0.162	Destabilizing	0.033	N	0.38	neutral	None	None	None	None	I
R/C	0.2569	likely_benign	0.286	benign	-0.574	Destabilizing	0.997	D	0.705	prob.neutral	None	None	None	None	I
R/D	0.8453	likely_pathogenic	0.8633	pathogenic	-0.687	Destabilizing	0.987	D	0.701	prob.neutral	None	None	None	None	I
R/E	0.5385	ambiguous	0.5546	ambiguous	-0.575	Destabilizing	0.916	D	0.61	neutral	None	None	None	None	I
R/F	0.7164	likely_pathogenic	0.7707	pathogenic	-0.281	Destabilizing	0.987	D	0.705	prob.neutral	None	None	None	None	I
R/G	0.4945	ambiguous	0.5103	ambiguous	-0.371	Destabilizing	0.805	D	0.601	neutral	D	0.523732693	None	None	I
R/H	0.1395	likely_benign	0.159	benign	-1.093	Destabilizing	0.999	D	0.649	neutral	None	None	None	None	I
R/I	0.5155	ambiguous	0.532	ambiguous	0.373	Stabilizing	0.967	D	0.707	prob.neutral	N	0.498093867	None	None	I
R/K	0.1433	likely_benign	0.1474	benign	-0.297	Destabilizing	0.773	D	0.576	neutral	N	0.501317193	None	None	I
R/L	0.4099	ambiguous	0.4234	ambiguous	0.373	Stabilizing	0.845	D	0.614	neutral	None	None	None	None	I
R/M	0.4748	ambiguous	0.4861	ambiguous	-0.342	Destabilizing	0.999	D	0.666	neutral	None	None	None	None	I
R/N	0.7615	likely_pathogenic	0.7891	pathogenic	-0.482	Destabilizing	0.987	D	0.641	neutral	None	None	None	None	I
R/P	0.4281	ambiguous	0.4366	ambiguous	0.213	Stabilizing	0.987	D	0.714	prob.delet.	None	None	None	None	I
R/Q	0.164	likely_benign	0.1704	benign	-0.381	Destabilizing	0.987	D	0.643	neutral	None	None	None	None	I
R/S	0.7134	likely_pathogenic	0.7451	pathogenic	-0.621	Destabilizing	0.805	D	0.615	neutral	D	0.523212618	None	None	I
R/T	0.5611	ambiguous	0.5777	pathogenic	-0.359	Destabilizing	0.892	D	0.651	neutral	N	0.479736122	None	None	I
R/V	0.5778	likely_pathogenic	0.6009	pathogenic	0.213	Stabilizing	0.95	D	0.635	neutral	None	None	None	None	I
R/W	0.3	likely_benign	0.334	benign	-0.43	Destabilizing	0.999	D	0.702	prob.neutral	None	None	None	None	I
R/Y	0.4883	ambiguous	0.5441	ambiguous	-0.054	Destabilizing	0.996	D	0.712	prob.delet.	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.