TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8665	26218;26219;26220	chr2:178715193;178715192;178715191	chr2:179579920;179579919;179579918
N2AB	8348	25267;25268;25269	chr2:178715193;178715192;178715191	chr2:179579920;179579919;179579918
N2A	7421	22486;22487;22488	chr2:178715193;178715192;178715191	chr2:179579920;179579919;179579918
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: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-72
• Domain position: 23
• Structural Position: 34
• Q(SASA): 0.1965
• 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
E/G	rs1226104343	-1.425	0.932	N	0.663	0.392	0.518147779662	gnomAD-2.1.1	8.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.77E-05	0
E/G	rs1226104343	-1.425	0.932	N	0.663	0.392	0.518147779662	gnomAD-4.0.0	1.91592E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.42875E-05	0	1.65651E-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
E/A	0.3033	likely_benign	0.2659	benign	-1.08	Destabilizing	0.804	D	0.534	neutral	N	0.489428993	None	None	N
E/C	0.9279	likely_pathogenic	0.9081	pathogenic	-0.678	Destabilizing	0.998	D	0.739	prob.delet.	None	None	None	None	N
E/D	0.4241	ambiguous	0.3715	ambiguous	-1.356	Destabilizing	0.345	N	0.478	neutral	N	0.497911689	None	None	N
E/F	0.8339	likely_pathogenic	0.787	pathogenic	-0.512	Destabilizing	0.995	D	0.761	deleterious	None	None	None	None	N
E/G	0.5066	ambiguous	0.4287	ambiguous	-1.487	Destabilizing	0.932	D	0.663	neutral	N	0.500166642	None	None	N
E/H	0.6397	likely_pathogenic	0.5753	pathogenic	-0.852	Destabilizing	0.994	D	0.594	neutral	None	None	None	None	N
E/I	0.3884	ambiguous	0.3453	ambiguous	0.055	Stabilizing	0.971	D	0.775	deleterious	None	None	None	None	N
E/K	0.2941	likely_benign	0.259	benign	-1.076	Destabilizing	0.023	N	0.43	neutral	N	0.514009637	None	None	N
E/L	0.4961	ambiguous	0.4423	ambiguous	0.055	Stabilizing	0.943	D	0.713	prob.delet.	None	None	None	None	N
E/M	0.529	ambiguous	0.481	ambiguous	0.621	Stabilizing	0.986	D	0.723	prob.delet.	None	None	None	None	N
E/N	0.5985	likely_pathogenic	0.5232	ambiguous	-1.453	Destabilizing	0.885	D	0.575	neutral	None	None	None	None	N
E/P	0.9749	likely_pathogenic	0.9557	pathogenic	-0.303	Destabilizing	0.833	D	0.689	prob.neutral	None	None	None	None	N
E/Q	0.177	likely_benign	0.1615	benign	-1.283	Destabilizing	0.844	D	0.497	neutral	N	0.518204735	None	None	N
E/R	0.4625	ambiguous	0.4014	ambiguous	-0.822	Destabilizing	0.068	N	0.377	neutral	None	None	None	None	N
E/S	0.3871	ambiguous	0.3365	benign	-1.927	Destabilizing	0.844	D	0.48	neutral	None	None	None	None	N
E/T	0.3732	ambiguous	0.3259	benign	-1.581	Destabilizing	0.963	D	0.659	neutral	None	None	None	None	N
E/V	0.2649	likely_benign	0.2333	benign	-0.303	Destabilizing	0.947	D	0.681	prob.neutral	N	0.491443682	None	None	N
E/W	0.956	likely_pathogenic	0.9375	pathogenic	-0.327	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
E/Y	0.7654	likely_pathogenic	0.7121	pathogenic	-0.273	Destabilizing	0.998	D	0.742	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.