TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4000	12223;12224;12225	chr2:178741235;178741234;178741233	chr2:179605962;179605961;179605960
N2AB	3683	11272;11273;11274	chr2:178741235;178741234;178741233	chr2:179605962;179605961;179605960
N2A	None	None	chr2:None	chr2:None
N2B	3637	11134;11135;11136	chr2:178741235;178741234;178741233	chr2:179605962;179605961;179605960
Novex-1	3762	11509;11510;11511	chr2:178741235;178741234;178741233	chr2:179605962;179605961;179605960
Novex-2	3829	11710;11711;11712	chr2:178741235;178741234;178741233	chr2:179605962;179605961;179605960
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-28
• Domain position: 63
• Structural Position: 143
• Q(SASA): 0.4992
• 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/E	None	None	0.334	N	0.313	0.024	None	gnomAD-4.0.0	6.84355E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99431E-07	0	0
D/G	rs938144456	None	0.201	N	0.289	0.107	None	gnomAD-4.0.0	1.59183E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85788E-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
D/A	0.3774	ambiguous	0.3952	ambiguous	-0.342	Destabilizing	0.201	N	0.319	neutral	N	0.452624287	None	None	I
D/C	0.8204	likely_pathogenic	0.8387	pathogenic	-0.079	Destabilizing	0.992	D	0.408	neutral	None	None	None	None	I
D/E	0.429	ambiguous	0.4314	ambiguous	-0.66	Destabilizing	0.334	N	0.313	neutral	N	0.453760573	None	None	I
D/F	0.7193	likely_pathogenic	0.7601	pathogenic	-0.412	Destabilizing	0.972	D	0.411	neutral	None	None	None	None	I
D/G	0.5012	ambiguous	0.5398	ambiguous	-0.618	Destabilizing	0.201	N	0.289	neutral	N	0.453658116	None	None	I
D/H	0.4536	ambiguous	0.5048	ambiguous	-0.82	Destabilizing	0.81	D	0.343	neutral	N	0.445061464	None	None	I
D/I	0.6561	likely_pathogenic	0.678	pathogenic	0.354	Stabilizing	0.85	D	0.425	neutral	None	None	None	None	I
D/K	0.6056	likely_pathogenic	0.6784	pathogenic	-0.352	Destabilizing	0.447	N	0.29	neutral	None	None	None	None	I
D/L	0.6465	likely_pathogenic	0.6755	pathogenic	0.354	Stabilizing	0.617	D	0.376	neutral	None	None	None	None	I
D/M	0.8544	likely_pathogenic	0.8621	pathogenic	0.741	Stabilizing	0.992	D	0.397	neutral	None	None	None	None	I
D/N	0.1583	likely_benign	0.1801	benign	-0.527	Destabilizing	0.002	N	0.121	neutral	N	0.439773629	None	None	I
D/P	0.9617	likely_pathogenic	0.9605	pathogenic	0.147	Stabilizing	0.92	D	0.345	neutral	None	None	None	None	I
D/Q	0.6198	likely_pathogenic	0.6479	pathogenic	-0.447	Destabilizing	0.85	D	0.349	neutral	None	None	None	None	I
D/R	0.5775	likely_pathogenic	0.6442	pathogenic	-0.328	Destabilizing	0.85	D	0.373	neutral	None	None	None	None	I
D/S	0.2463	likely_benign	0.2703	benign	-0.716	Destabilizing	0.026	N	0.131	neutral	None	None	None	None	I
D/T	0.547	ambiguous	0.5642	pathogenic	-0.51	Destabilizing	0.021	N	0.191	neutral	None	None	None	None	I
D/V	0.4831	ambiguous	0.4986	ambiguous	0.147	Stabilizing	0.549	D	0.352	neutral	N	0.477671441	None	None	I
D/W	0.9533	likely_pathogenic	0.957	pathogenic	-0.401	Destabilizing	0.992	D	0.551	neutral	None	None	None	None	I
D/Y	0.2635	likely_benign	0.3188	benign	-0.238	Destabilizing	0.963	D	0.41	neutral	N	0.447992376	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.