TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	956	3091;3092;3093	chr2:178783040;178783039;178783038	chr2:179647767;179647766;179647765
N2AB	956	3091;3092;3093	chr2:178783040;178783039;178783038	chr2:179647767;179647766;179647765
N2A	956	3091;3092;3093	chr2:178783040;178783039;178783038	chr2:179647767;179647766;179647765
N2B	910	2953;2954;2955	chr2:178783040;178783039;178783038	chr2:179647767;179647766;179647765
Novex-1	910	2953;2954;2955	chr2:178783040;178783039;178783038	chr2:179647767;179647766;179647765
Novex-2	910	2953;2954;2955	chr2:178783040;178783039;178783038	chr2:179647767;179647766;179647765
Novex-3	956	3091;3092;3093	chr2:178783040;178783039;178783038	chr2:179647767;179647766;179647765

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-3
• Domain position: 14
• Structural Position: 23
• Q(SASA): 0.434
• 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/V	rs1256742632	-0.148	1.0	N	0.689	0.565	0.710140478693	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	1.14837E-04	0	None	0	0	None	0	None	0	0	0
E/V	rs1256742632	-0.148	1.0	N	0.689	0.565	0.710140478693	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	6.33473E-05	0	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	0.751	likely_pathogenic	0.8108	pathogenic	-0.778	Destabilizing	0.999	D	0.58	neutral	N	0.511264372	None	None	N
E/C	0.9971	likely_pathogenic	0.9977	pathogenic	-0.38	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
E/D	0.9366	likely_pathogenic	0.9572	pathogenic	-0.705	Destabilizing	0.999	D	0.412	neutral	N	0.520620259	None	None	N
E/F	0.999	likely_pathogenic	0.9993	pathogenic	-0.155	Destabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	N
E/G	0.9157	likely_pathogenic	0.9393	pathogenic	-1.091	Destabilizing	1.0	D	0.629	neutral	D	0.698406898	None	None	N
E/H	0.9921	likely_pathogenic	0.9948	pathogenic	-0.074	Destabilizing	1.0	D	0.631	neutral	None	None	None	None	N
E/I	0.9846	likely_pathogenic	0.9891	pathogenic	0.062	Stabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
E/K	0.8873	likely_pathogenic	0.9297	pathogenic	-0.085	Destabilizing	0.999	D	0.565	neutral	N	0.515839153	None	None	N
E/L	0.9886	likely_pathogenic	0.9925	pathogenic	0.062	Stabilizing	1.0	D	0.71	prob.delet.	None	None	None	None	N
E/M	0.9864	likely_pathogenic	0.9903	pathogenic	0.276	Stabilizing	1.0	D	0.65	neutral	None	None	None	None	N
E/N	0.9792	likely_pathogenic	0.9862	pathogenic	-0.717	Destabilizing	1.0	D	0.684	prob.neutral	None	None	None	None	N
E/P	0.9674	likely_pathogenic	0.9762	pathogenic	-0.197	Destabilizing	1.0	D	0.632	neutral	None	None	None	None	N
E/Q	0.7183	likely_pathogenic	0.7791	pathogenic	-0.611	Destabilizing	1.0	D	0.607	neutral	D	0.577583458	None	None	N
E/R	0.9286	likely_pathogenic	0.953	pathogenic	0.275	Stabilizing	1.0	D	0.675	neutral	None	None	None	None	N
E/S	0.8959	likely_pathogenic	0.9249	pathogenic	-0.931	Destabilizing	0.999	D	0.629	neutral	None	None	None	None	N
E/T	0.9436	likely_pathogenic	0.9631	pathogenic	-0.662	Destabilizing	1.0	D	0.652	neutral	None	None	None	None	N
E/V	0.9479	likely_pathogenic	0.963	pathogenic	-0.197	Destabilizing	1.0	D	0.689	prob.neutral	N	0.510597293	None	None	N
E/W	0.9996	likely_pathogenic	0.9997	pathogenic	0.184	Stabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
E/Y	0.9977	likely_pathogenic	0.9983	pathogenic	0.136	Stabilizing	1.0	D	0.679	prob.neutral	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.