TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7873	23842;23843;23844	chr2:178720025;178720024;178720023	chr2:179584752;179584751;179584750
N2AB	7556	22891;22892;22893	chr2:178720025;178720024;178720023	chr2:179584752;179584751;179584750
N2A	6629	20110;20111;20112	chr2:178720025;178720024;178720023	chr2:179584752;179584751;179584750
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: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-63
• Domain position: 79
• Structural Position: 162
• Q(SASA): 1.086
• 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
D/G	None	None	0.801	D	0.382	0.259	0.365892764245	gnomAD-4.0.0	1.59325E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.4339E-05	0
D/N	rs753929851	0.579	0.233	N	0.375	0.208	0.33110744837	gnomAD-2.1.1	7.17E-06	None	None	None	None	I	None	8.3E-05	0	None	0	0	None	0	None	0	0	0
D/N	rs753929851	0.579	0.233	N	0.375	0.208	0.33110744837	gnomAD-3.1.2	1.31E-05	None	None	None	None	I	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
D/N	rs753929851	0.579	0.233	N	0.375	0.208	0.33110744837	gnomAD-4.0.0	4.34016E-06	None	None	None	None	I	None	8.01475E-05	0	None	0	0	None	0	0	0	0	1.60231E-05

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
D/A	0.3918	ambiguous	0.2892	benign	0.047	Stabilizing	0.801	D	0.428	neutral	N	0.498482824	None	None	I
D/C	0.9336	likely_pathogenic	0.8883	pathogenic	0.082	Stabilizing	0.998	D	0.489	neutral	None	None	None	None	I
D/E	0.2139	likely_benign	0.1931	benign	-0.294	Destabilizing	0.005	N	0.232	neutral	N	0.460577796	None	None	I
D/F	0.8806	likely_pathogenic	0.8044	pathogenic	-0.155	Destabilizing	0.991	D	0.435	neutral	None	None	None	None	I
D/G	0.4976	ambiguous	0.3643	ambiguous	-0.051	Destabilizing	0.801	D	0.382	neutral	D	0.532307396	None	None	I
D/H	0.6445	likely_pathogenic	0.5365	ambiguous	0.324	Stabilizing	0.986	D	0.401	neutral	N	0.495834547	None	None	I
D/I	0.6634	likely_pathogenic	0.5653	pathogenic	0.233	Stabilizing	0.974	D	0.437	neutral	None	None	None	None	I
D/K	0.7185	likely_pathogenic	0.6622	pathogenic	0.526	Stabilizing	0.728	D	0.401	neutral	None	None	None	None	I
D/L	0.7184	likely_pathogenic	0.6296	pathogenic	0.233	Stabilizing	0.949	D	0.406	neutral	None	None	None	None	I
D/M	0.8621	likely_pathogenic	0.7988	pathogenic	0.159	Stabilizing	0.998	D	0.443	neutral	None	None	None	None	I
D/N	0.2245	likely_benign	0.1727	benign	0.396	Stabilizing	0.233	N	0.375	neutral	N	0.487667793	None	None	I
D/P	0.8958	likely_pathogenic	0.8483	pathogenic	0.19	Stabilizing	0.974	D	0.391	neutral	None	None	None	None	I
D/Q	0.6387	likely_pathogenic	0.5629	ambiguous	0.373	Stabilizing	0.325	N	0.365	neutral	None	None	None	None	I
D/R	0.7618	likely_pathogenic	0.6972	pathogenic	0.647	Stabilizing	0.949	D	0.419	neutral	None	None	None	None	I
D/S	0.2926	likely_benign	0.2163	benign	0.295	Stabilizing	0.842	D	0.402	neutral	None	None	None	None	I
D/T	0.5118	ambiguous	0.4148	ambiguous	0.372	Stabilizing	0.842	D	0.419	neutral	None	None	None	None	I
D/V	0.4559	ambiguous	0.3638	ambiguous	0.19	Stabilizing	0.966	D	0.414	neutral	N	0.520975681	None	None	I
D/W	0.9798	likely_pathogenic	0.9667	pathogenic	-0.15	Destabilizing	0.998	D	0.543	neutral	None	None	None	None	I
D/Y	0.6003	likely_pathogenic	0.4781	ambiguous	0.062	Stabilizing	0.996	D	0.435	neutral	N	0.496088037	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.