TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	36	331;332;333	chr2:178802327;178802326;178802325	chr2:179667054;179667053;179667052
N2AB	36	331;332;333	chr2:178802327;178802326;178802325	chr2:179667054;179667053;179667052
N2A	36	331;332;333	chr2:178802327;178802326;178802325	chr2:179667054;179667053;179667052
N2B	36	331;332;333	chr2:178802327;178802326;178802325	chr2:179667054;179667053;179667052
Novex-1	36	331;332;333	chr2:178802327;178802326;178802325	chr2:179667054;179667053;179667052
Novex-2	36	331;332;333	chr2:178802327;178802326;178802325	chr2:179667054;179667053;179667052
Novex-3	36	331;332;333	chr2:178802327;178802326;178802325	chr2:179667054;179667053;179667052

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-1
• Domain position: 31
• Structural Position: 45
• Q(SASA): 0.7461
• 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/K	rs2094110497	None	0.996	N	0.657	0.517	0.488407942198	gnomAD-4.0.0	1.59079E-06	None	None	None	-0.214(TCAP)	N	None	0	2.28666E-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	0.2143	likely_benign	0.2	benign	-0.417	Destabilizing	0.992	D	0.707	prob.neutral	N	0.51110913	None	-0.389(TCAP)	N
E/C	0.9848	likely_pathogenic	0.9789	pathogenic	-0.106	Destabilizing	1.0	D	0.776	deleterious	None	None	None	-0.471(TCAP)	N
E/D	0.2509	likely_benign	0.2352	benign	-0.538	Destabilizing	0.941	D	0.528	neutral	N	0.511456543	None	-0.427(TCAP)	N
E/F	0.9427	likely_pathogenic	0.9239	pathogenic	-0.181	Destabilizing	1.0	D	0.752	deleterious	None	None	None	-0.311(TCAP)	N
E/G	0.3679	ambiguous	0.3395	benign	-0.654	Destabilizing	0.999	D	0.683	prob.neutral	D	0.622967489	None	-0.558(TCAP)	N
E/H	0.7043	likely_pathogenic	0.6719	pathogenic	-0.019	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	0.488(TCAP)	N
E/I	0.6556	likely_pathogenic	0.5891	pathogenic	0.184	Stabilizing	0.998	D	0.765	deleterious	None	None	None	0.106(TCAP)	N
E/K	0.2338	likely_benign	0.2227	benign	0.229	Stabilizing	0.996	D	0.657	neutral	N	0.491361187	None	-0.214(TCAP)	N
E/L	0.6804	likely_pathogenic	0.6319	pathogenic	0.184	Stabilizing	0.998	D	0.758	deleterious	None	None	None	0.106(TCAP)	N
E/M	0.6895	likely_pathogenic	0.6337	pathogenic	0.283	Stabilizing	0.997	D	0.721	prob.delet.	None	None	None	0.896(TCAP)	N
E/N	0.418	ambiguous	0.3836	ambiguous	-0.192	Destabilizing	0.996	D	0.733	prob.delet.	None	None	None	-1.789(TCAP)	N
E/P	0.9422	likely_pathogenic	0.9372	pathogenic	0.004	Stabilizing	0.987	D	0.758	deleterious	None	None	None	-0.054(TCAP)	N
E/Q	0.1796	likely_benign	0.1736	benign	-0.128	Destabilizing	0.998	D	0.65	neutral	N	0.512650861	None	-1.186(TCAP)	N
E/R	0.3979	ambiguous	0.3808	ambiguous	0.47	Stabilizing	0.999	D	0.725	prob.delet.	None	None	None	-0.195(TCAP)	N
E/S	0.263	likely_benign	0.2445	benign	-0.343	Destabilizing	0.994	D	0.698	prob.neutral	None	None	None	-1.544(TCAP)	N
E/T	0.2751	likely_benign	0.2473	benign	-0.146	Destabilizing	0.999	D	0.744	deleterious	None	None	None	-1.362(TCAP)	N
E/V	0.367	ambiguous	0.3274	benign	0.004	Stabilizing	0.996	D	0.741	deleterious	N	0.512898898	None	-0.054(TCAP)	N
E/W	0.9824	likely_pathogenic	0.9781	pathogenic	0.004	Stabilizing	1.0	D	0.777	deleterious	None	None	None	-0.502(TCAP)	N
E/Y	0.9059	likely_pathogenic	0.8798	pathogenic	0.075	Stabilizing	1.0	D	0.746	deleterious	None	None	None	-0.363(TCAP)	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.