TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3889	11890;11891;11892	chr2:178741568;178741567;178741566	chr2:179606295;179606294;179606293
N2AB	3572	10939;10940;10941	chr2:178741568;178741567;178741566	chr2:179606295;179606294;179606293
N2A	None	None	chr2:None	chr2:None
N2B	3526	10801;10802;10803	chr2:178741568;178741567;178741566	chr2:179606295;179606294;179606293
Novex-1	3651	11176;11177;11178	chr2:178741568;178741567;178741566	chr2:179606295;179606294;179606293
Novex-2	3718	11377;11378;11379	chr2:178741568;178741567;178741566	chr2:179606295;179606294;179606293
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-27
• Domain position: 70
• Structural Position: 153
• Q(SASA): 0.4434
• 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	0.645	N	0.589	0.313	None	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.625E-06	0	0
E/D	rs377423256	-0.874	0.006	N	0.391	0.091	None	gnomAD-2.1.1	1.43E-05	None	None	None	None	I	None	1.24018E-04	2.83E-05	None	0	0	None	0	None	0	0	0
E/D	rs377423256	-0.874	0.006	N	0.391	0.091	None	gnomAD-3.1.2	5.92E-05	None	None	None	None	I	None	1.93218E-04	0	0	0	0	None	0	0	0	0	4.77555E-04
E/D	rs377423256	-0.874	0.006	N	0.391	0.091	None	gnomAD-4.0.0	1.05351E-05	None	None	None	None	I	None	1.86986E-04	1.66767E-05	None	0	0	None	0	0	0	0	3.20195E-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	0.2243	likely_benign	0.2194	benign	-1.323	Destabilizing	0.645	D	0.589	neutral	N	0.512583814	None	None	I
E/C	0.8894	likely_pathogenic	0.879	pathogenic	-0.592	Destabilizing	0.995	D	0.662	neutral	None	None	None	None	I
E/D	0.2591	likely_benign	0.2455	benign	-1.071	Destabilizing	0.006	N	0.391	neutral	N	0.511787403	None	None	I
E/F	0.7478	likely_pathogenic	0.7538	pathogenic	-0.703	Destabilizing	0.995	D	0.723	prob.delet.	None	None	None	None	I
E/G	0.3157	likely_benign	0.2991	benign	-1.717	Destabilizing	0.645	D	0.653	neutral	D	0.634152996	None	None	I
E/H	0.575	likely_pathogenic	0.5785	pathogenic	-0.903	Destabilizing	0.995	D	0.637	neutral	None	None	None	None	I
E/I	0.3127	likely_benign	0.318	benign	-0.22	Destabilizing	0.945	D	0.741	deleterious	None	None	None	None	I
E/K	0.1386	likely_benign	0.136	benign	-0.669	Destabilizing	0.006	N	0.402	neutral	N	0.503739005	None	None	I
E/L	0.4407	ambiguous	0.4367	ambiguous	-0.22	Destabilizing	0.894	D	0.738	prob.delet.	None	None	None	None	I
E/M	0.4336	ambiguous	0.4321	ambiguous	0.441	Stabilizing	0.995	D	0.703	prob.neutral	None	None	None	None	I
E/N	0.3435	ambiguous	0.3317	benign	-1.201	Destabilizing	0.809	D	0.635	neutral	None	None	None	None	I
E/P	0.7643	likely_pathogenic	0.7887	pathogenic	-0.569	Destabilizing	0.945	D	0.744	deleterious	None	None	None	None	I
E/Q	0.1745	likely_benign	0.18	benign	-1.045	Destabilizing	0.864	D	0.596	neutral	N	0.510546257	None	None	I
E/R	0.2598	likely_benign	0.2679	benign	-0.444	Destabilizing	0.809	D	0.633	neutral	None	None	None	None	I
E/S	0.3051	likely_benign	0.3026	benign	-1.653	Destabilizing	0.547	D	0.529	neutral	None	None	None	None	I
E/T	0.2712	likely_benign	0.2679	benign	-1.294	Destabilizing	0.894	D	0.713	prob.delet.	None	None	None	None	I
E/V	0.2236	likely_benign	0.2236	benign	-0.569	Destabilizing	0.928	D	0.733	prob.delet.	N	0.472286066	None	None	I
E/W	0.9057	likely_pathogenic	0.9109	pathogenic	-0.348	Destabilizing	0.995	D	0.658	neutral	None	None	None	None	I
E/Y	0.6454	likely_pathogenic	0.6484	pathogenic	-0.389	Destabilizing	0.981	D	0.724	prob.delet.	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.