TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30010	90253;90254;90255	chr2:178552872;178552871;178552870	chr2:179417599;179417598;179417597
N2AB	28369	85330;85331;85332	chr2:178552872;178552871;178552870	chr2:179417599;179417598;179417597
N2A	27442	82549;82550;82551	chr2:178552872;178552871;178552870	chr2:179417599;179417598;179417597
N2B	20945	63058;63059;63060	chr2:178552872;178552871;178552870	chr2:179417599;179417598;179417597
Novex-1	21070	63433;63434;63435	chr2:178552872;178552871;178552870	chr2:179417599;179417598;179417597
Novex-2	21137	63634;63635;63636	chr2:178552872;178552871;178552870	chr2:179417599;179417598;179417597
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-106
• Domain position: 78
• Structural Position: 111
• Q(SASA): 0.2578
• 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
E/A	None	None	0.201	N	0.521	0.185	0.276065633971	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05
E/D	rs1481370261	None	0.504	N	0.403	0.19	0.209622950755	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
E/D	rs1481370261	None	0.504	N	0.403	0.19	0.209622950755	gnomAD-4.0.0	6.57091E-06	None	None	None	None	I	None	0	6.54879E-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
E/A	0.3446	ambiguous	0.2727	benign	-1.211	Destabilizing	0.201	N	0.521	neutral	N	0.482013847	None	None	I
E/C	0.8919	likely_pathogenic	0.862	pathogenic	-0.768	Destabilizing	0.947	D	0.809	deleterious	None	None	None	None	I
E/D	0.8168	likely_pathogenic	0.7882	pathogenic	-1.537	Destabilizing	0.504	D	0.403	neutral	N	0.515312749	None	None	I
E/F	0.929	likely_pathogenic	0.8993	pathogenic	-1.09	Destabilizing	0.7	D	0.837	deleterious	None	None	None	None	I
E/G	0.5477	ambiguous	0.4638	ambiguous	-1.578	Destabilizing	0.781	D	0.727	prob.delet.	N	0.510539809	None	None	I
E/H	0.8308	likely_pathogenic	0.7888	pathogenic	-1.275	Destabilizing	0.982	D	0.685	prob.neutral	None	None	None	None	I
E/I	0.5308	ambiguous	0.4174	ambiguous	-0.195	Destabilizing	0.287	N	0.762	deleterious	None	None	None	None	I
E/K	0.3401	ambiguous	0.2603	benign	-1.032	Destabilizing	0.504	D	0.443	neutral	N	0.483027805	None	None	I
E/L	0.7656	likely_pathogenic	0.675	pathogenic	-0.195	Destabilizing	0.25	N	0.707	prob.neutral	None	None	None	None	I
E/M	0.6371	likely_pathogenic	0.5324	ambiguous	0.405	Stabilizing	0.898	D	0.805	deleterious	None	None	None	None	I
E/N	0.8159	likely_pathogenic	0.7569	pathogenic	-1.344	Destabilizing	0.935	D	0.694	prob.neutral	None	None	None	None	I
E/P	0.996	likely_pathogenic	0.9946	pathogenic	-0.514	Destabilizing	0.935	D	0.819	deleterious	None	None	None	None	I
E/Q	0.1857	likely_benign	0.1482	benign	-1.2	Destabilizing	0.916	D	0.631	neutral	N	0.47683606	None	None	I
E/R	0.508	ambiguous	0.4216	ambiguous	-0.895	Destabilizing	0.826	D	0.706	prob.neutral	None	None	None	None	I
E/S	0.5166	ambiguous	0.445	ambiguous	-1.844	Destabilizing	0.399	N	0.506	neutral	None	None	None	None	I
E/T	0.5348	ambiguous	0.4576	ambiguous	-1.514	Destabilizing	0.539	D	0.735	prob.delet.	None	None	None	None	I
E/V	0.2772	likely_benign	0.2012	benign	-0.514	Destabilizing	0.004	N	0.391	neutral	N	0.460425002	None	None	I
E/W	0.9833	likely_pathogenic	0.9767	pathogenic	-1.029	Destabilizing	0.982	D	0.792	deleterious	None	None	None	None	I
E/Y	0.9176	likely_pathogenic	0.8877	pathogenic	-0.851	Destabilizing	0.826	D	0.833	deleterious	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.