TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5866	17821;17822;17823	chr2:178731069;178731068;178731067	chr2:179595796;179595795;179595794
N2AB	5549	16870;16871;16872	chr2:178731069;178731068;178731067	chr2:179595796;179595795;179595794
N2A	4622	14089;14090;14091	chr2:178731069;178731068;178731067	chr2:179595796;179595795;179595794
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: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Ig-42
• Domain position: 44
• Structural Position: 73
• Q(SASA): 0.3546
• 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
G/C	rs753136638	-0.619	0.999	N	0.758	0.42	0.548443230319	gnomAD-2.1.1	8.03E-05	None	None	None	None	N	None	0	4.63768E-04	None	0	0	None	0	None	0	1.77E-05	3.30688E-04
G/C	rs753136638	-0.619	0.999	N	0.758	0.42	0.548443230319	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	1.31148E-04	0	0	0	None	0	0	1.47E-05	0	0
G/C	rs753136638	-0.619	0.999	N	0.758	0.42	0.548443230319	gnomAD-4.0.0	1.73544E-05	None	None	None	None	N	None	4.00919E-05	3.0019E-04	None	0	0	None	0	0	5.93371E-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
G/A	0.1495	likely_benign	0.1892	benign	-0.139	Destabilizing	0.865	D	0.483	neutral	N	0.510717749	None	None	N
G/C	0.2152	likely_benign	0.3277	benign	-0.879	Destabilizing	0.999	D	0.758	deleterious	N	0.473243846	None	None	N
G/D	0.15	likely_benign	0.2251	benign	0.047	Stabilizing	0.978	D	0.702	prob.neutral	N	0.469772417	None	None	N
G/E	0.2653	likely_benign	0.4193	ambiguous	-0.073	Destabilizing	0.983	D	0.719	prob.delet.	None	None	None	None	N
G/F	0.6044	likely_pathogenic	0.7558	pathogenic	-0.671	Destabilizing	0.998	D	0.773	deleterious	None	None	None	None	N
G/H	0.3851	ambiguous	0.5263	ambiguous	-0.302	Destabilizing	0.998	D	0.734	prob.delet.	None	None	None	None	N
G/I	0.3972	ambiguous	0.6098	pathogenic	-0.175	Destabilizing	0.998	D	0.773	deleterious	None	None	None	None	N
G/K	0.5609	ambiguous	0.7352	pathogenic	-0.607	Destabilizing	0.968	D	0.717	prob.delet.	None	None	None	None	N
G/L	0.4319	ambiguous	0.5921	pathogenic	-0.175	Destabilizing	0.983	D	0.735	prob.delet.	None	None	None	None	N
G/M	0.5649	likely_pathogenic	0.7072	pathogenic	-0.499	Destabilizing	0.999	D	0.757	deleterious	None	None	None	None	N
G/N	0.2177	likely_benign	0.2847	benign	-0.367	Destabilizing	0.968	D	0.731	prob.delet.	None	None	None	None	N
G/P	0.8325	likely_pathogenic	0.9275	pathogenic	-0.13	Destabilizing	0.992	D	0.758	deleterious	None	None	None	None	N
G/Q	0.4041	ambiguous	0.5497	ambiguous	-0.512	Destabilizing	0.983	D	0.766	deleterious	None	None	None	None	N
G/R	0.434	ambiguous	0.6295	pathogenic	-0.327	Destabilizing	0.978	D	0.755	deleterious	N	0.463836097	None	None	N
G/S	0.0839	likely_benign	0.0917	benign	-0.612	Destabilizing	0.146	N	0.409	neutral	N	0.431136671	None	None	N
G/T	0.1533	likely_benign	0.1923	benign	-0.636	Destabilizing	0.968	D	0.719	prob.delet.	None	None	None	None	N
G/V	0.2656	likely_benign	0.4315	ambiguous	-0.13	Destabilizing	0.978	D	0.745	deleterious	N	0.491094611	None	None	N
G/W	0.5228	ambiguous	0.6616	pathogenic	-0.873	Destabilizing	0.999	D	0.745	deleterious	None	None	None	None	N
G/Y	0.4525	ambiguous	0.6406	pathogenic	-0.499	Destabilizing	0.999	D	0.777	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.