TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6239	18940;18941;18942	chr2:178729441;178729440;178729439	chr2:179594168;179594167;179594166
N2AB	5922	17989;17990;17991	chr2:178729441;178729440;178729439	chr2:179594168;179594167;179594166
N2A	4995	15208;15209;15210	chr2:178729441;178729440;178729439	chr2:179594168;179594167;179594166
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: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-46
• Domain position: 41
• Structural Position: 58
• Q(SASA): 0.1187
• 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
I/M	None	None	0.58	N	0.379	0.342	0.41958645093	gnomAD-4.0.0	1.59165E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85914E-06	0	0
I/S	rs1221710663	-2.808	0.991	D	0.719	0.695	0.905720156449	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
I/S	rs1221710663	-2.808	0.991	D	0.719	0.695	0.905720156449	gnomAD-4.0.0	1.59163E-06	None	None	None	None	N	None	0	2.2876E-05	None	0	0	None	0	0	0	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
I/A	0.9015	likely_pathogenic	0.9231	pathogenic	-2.267	Highly Destabilizing	0.953	D	0.549	neutral	None	None	None	None	N
I/C	0.9409	likely_pathogenic	0.9633	pathogenic	-1.461	Destabilizing	0.999	D	0.708	prob.delet.	None	None	None	None	N
I/D	0.9936	likely_pathogenic	0.9943	pathogenic	-2.696	Highly Destabilizing	0.998	D	0.822	deleterious	None	None	None	None	N
I/E	0.9781	likely_pathogenic	0.9787	pathogenic	-2.448	Highly Destabilizing	0.993	D	0.813	deleterious	None	None	None	None	N
I/F	0.4033	ambiguous	0.4356	ambiguous	-1.409	Destabilizing	0.982	D	0.633	neutral	N	0.49554874	None	None	N
I/G	0.9736	likely_pathogenic	0.979	pathogenic	-2.798	Highly Destabilizing	0.993	D	0.805	deleterious	None	None	None	None	N
I/H	0.9667	likely_pathogenic	0.9703	pathogenic	-2.232	Highly Destabilizing	0.999	D	0.805	deleterious	None	None	None	None	N
I/K	0.9484	likely_pathogenic	0.9478	pathogenic	-1.785	Destabilizing	0.986	D	0.811	deleterious	None	None	None	None	N
I/L	0.1482	likely_benign	0.1646	benign	-0.728	Destabilizing	0.322	N	0.363	neutral	N	0.469946641	None	None	N
I/M	0.1576	likely_benign	0.1666	benign	-0.637	Destabilizing	0.58	D	0.379	neutral	N	0.497105676	None	None	N
I/N	0.9184	likely_pathogenic	0.9251	pathogenic	-2.233	Highly Destabilizing	0.997	D	0.825	deleterious	D	0.539354574	None	None	N
I/P	0.9817	likely_pathogenic	0.9834	pathogenic	-1.224	Destabilizing	0.998	D	0.825	deleterious	None	None	None	None	N
I/Q	0.9518	likely_pathogenic	0.9564	pathogenic	-2.051	Highly Destabilizing	0.993	D	0.826	deleterious	None	None	None	None	N
I/R	0.934	likely_pathogenic	0.9347	pathogenic	-1.62	Destabilizing	0.993	D	0.823	deleterious	None	None	None	None	N
I/S	0.9352	likely_pathogenic	0.9467	pathogenic	-2.864	Highly Destabilizing	0.991	D	0.719	prob.delet.	D	0.527491289	None	None	N
I/T	0.9076	likely_pathogenic	0.9279	pathogenic	-2.46	Highly Destabilizing	0.939	D	0.663	neutral	D	0.53605921	None	None	N
I/V	0.1622	likely_benign	0.202	benign	-1.224	Destabilizing	0.58	D	0.401	neutral	N	0.488537976	None	None	N
I/W	0.9491	likely_pathogenic	0.9511	pathogenic	-1.778	Destabilizing	0.999	D	0.787	deleterious	None	None	None	None	N
I/Y	0.8571	likely_pathogenic	0.8639	pathogenic	-1.434	Destabilizing	0.993	D	0.728	prob.delet.	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.