TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8775	26548;26549;26550	chr2:178714451;178714450;178714449	chr2:179579178;179579177;179579176
N2AB	8458	25597;25598;25599	chr2:178714451;178714450;178714449	chr2:179579178;179579177;179579176
N2A	7531	22816;22817;22818	chr2:178714451;178714450;178714449	chr2:179579178;179579177;179579176
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: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-73
• Domain position: 40
• Structural Position: 56
• Q(SASA): 0.4034
• 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/A	rs758590305	-0.516	0.884	N	0.521	0.377	0.413113201963	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.94E-06	0
E/A	rs758590305	-0.516	0.884	N	0.521	0.377	0.413113201963	gnomAD-4.0.0	1.59164E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85884E-06	0	0
E/D	None	None	0.288	N	0.484	0.166	0.282575091529	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-05	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	0.1832	likely_benign	0.2354	benign	-0.635	Destabilizing	0.884	D	0.521	neutral	N	0.494215159	None	None	N
E/C	0.8462	likely_pathogenic	0.8892	pathogenic	-0.258	Destabilizing	0.998	D	0.717	prob.delet.	None	None	None	None	N
E/D	0.1024	likely_benign	0.1001	benign	-0.594	Destabilizing	0.288	N	0.484	neutral	N	0.495229117	None	None	N
E/F	0.6631	likely_pathogenic	0.7522	pathogenic	-0.213	Destabilizing	0.985	D	0.673	neutral	None	None	None	None	N
E/G	0.191	likely_benign	0.2574	benign	-0.905	Destabilizing	0.962	D	0.519	neutral	N	0.517056355	None	None	N
E/H	0.4499	ambiguous	0.5186	ambiguous	-0.113	Destabilizing	0.02	N	0.203	neutral	None	None	None	None	N
E/I	0.2976	likely_benign	0.3753	ambiguous	0.074	Stabilizing	0.989	D	0.67	neutral	None	None	None	None	N
E/K	0.16	likely_benign	0.2233	benign	0.065	Stabilizing	0.874	D	0.512	neutral	D	0.530517884	None	None	N
E/L	0.3794	ambiguous	0.4723	ambiguous	0.074	Stabilizing	0.968	D	0.565	neutral	None	None	None	None	N
E/M	0.3913	ambiguous	0.4879	ambiguous	0.239	Stabilizing	0.984	D	0.657	neutral	None	None	None	None	N
E/N	0.1985	likely_benign	0.231	benign	-0.472	Destabilizing	0.667	D	0.489	neutral	None	None	None	None	N
E/P	0.714	likely_pathogenic	0.754	pathogenic	-0.141	Destabilizing	0.933	D	0.588	neutral	None	None	None	None	N
E/Q	0.1493	likely_benign	0.1897	benign	-0.384	Destabilizing	0.91	D	0.473	neutral	N	0.482805947	None	None	N
E/R	0.2776	likely_benign	0.3612	ambiguous	0.348	Stabilizing	0.902	D	0.472	neutral	None	None	None	None	N
E/S	0.2161	likely_benign	0.2664	benign	-0.641	Destabilizing	0.91	D	0.485	neutral	None	None	None	None	N
E/T	0.2352	likely_benign	0.3007	benign	-0.411	Destabilizing	0.98	D	0.519	neutral	None	None	None	None	N
E/V	0.1917	likely_benign	0.2413	benign	-0.141	Destabilizing	0.98	D	0.55	neutral	N	0.490874251	None	None	N
E/W	0.8405	likely_pathogenic	0.8929	pathogenic	0.052	Stabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
E/Y	0.5309	ambiguous	0.615	pathogenic	0.054	Stabilizing	0.989	D	0.568	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.