TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33553	100882;100883;100884	chr2:178536090;178536089;178536088	chr2:179400817;179400816;179400815
N2AB	31912	95959;95960;95961	chr2:178536090;178536089;178536088	chr2:179400817;179400816;179400815
N2A	30985	93178;93179;93180	chr2:178536090;178536089;178536088	chr2:179400817;179400816;179400815
N2B	24488	73687;73688;73689	chr2:178536090;178536089;178536088	chr2:179400817;179400816;179400815
Novex-1	24613	74062;74063;74064	chr2:178536090;178536089;178536088	chr2:179400817;179400816;179400815
Novex-2	24680	74263;74264;74265	chr2:178536090;178536089;178536088	chr2:179400817;179400816;179400815
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Ig-158
• Domain position: 58
• Structural Position: 136
• Q(SASA): 0.1409
• 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
H/Q	rs746903660	-1.683	0.951	N	0.678	0.341	0.380564188046	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
H/Q	rs746903660	-1.683	0.951	N	0.678	0.341	0.380564188046	gnomAD-4.0.0	6.16959E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.11027E-06	0	0
H/Y	rs1575305295	None	0.002	N	0.375	0.222	0.227934060464	gnomAD-4.0.0	1.59814E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.87485E-06	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
H/A	0.9116	likely_pathogenic	0.8364	pathogenic	-1.971	Destabilizing	0.897	D	0.659	neutral	None	None	None	None	N
H/C	0.4232	ambiguous	0.3687	ambiguous	-1.112	Destabilizing	0.995	D	0.718	prob.delet.	None	None	None	None	N
H/D	0.9492	likely_pathogenic	0.9223	pathogenic	-1.979	Destabilizing	0.801	D	0.655	neutral	N	0.493517143	None	None	N
H/E	0.9395	likely_pathogenic	0.9035	pathogenic	-1.77	Destabilizing	0.88	D	0.656	neutral	None	None	None	None	N
H/F	0.5937	likely_pathogenic	0.538	ambiguous	0.114	Stabilizing	0.709	D	0.622	neutral	None	None	None	None	N
H/G	0.9566	likely_pathogenic	0.9242	pathogenic	-2.401	Highly Destabilizing	0.947	D	0.676	prob.neutral	None	None	None	None	N
H/I	0.8409	likely_pathogenic	0.7737	pathogenic	-0.68	Destabilizing	0.924	D	0.722	prob.delet.	None	None	None	None	N
H/K	0.8985	likely_pathogenic	0.8522	pathogenic	-1.328	Destabilizing	0.777	D	0.637	neutral	None	None	None	None	N
H/L	0.533	ambiguous	0.4859	ambiguous	-0.68	Destabilizing	0.568	D	0.679	prob.neutral	D	0.522071759	None	None	N
H/M	0.9018	likely_pathogenic	0.8639	pathogenic	-0.874	Destabilizing	0.987	D	0.691	prob.neutral	None	None	None	None	N
H/N	0.5556	ambiguous	0.5027	ambiguous	-2.067	Highly Destabilizing	0.801	D	0.669	neutral	N	0.511644122	None	None	N
H/P	0.9842	likely_pathogenic	0.9701	pathogenic	-1.103	Destabilizing	0.977	D	0.703	prob.neutral	N	0.500860977	None	None	N
H/Q	0.6765	likely_pathogenic	0.6055	pathogenic	-1.633	Destabilizing	0.951	D	0.678	prob.neutral	N	0.509238535	None	None	N
H/R	0.6586	likely_pathogenic	0.5898	pathogenic	-1.58	Destabilizing	0.842	D	0.663	neutral	N	0.513356276	None	None	N
H/S	0.7713	likely_pathogenic	0.6871	pathogenic	-2.173	Highly Destabilizing	0.897	D	0.641	neutral	None	None	None	None	N
H/T	0.8545	likely_pathogenic	0.7654	pathogenic	-1.845	Destabilizing	0.842	D	0.691	prob.neutral	None	None	None	None	N
H/V	0.7861	likely_pathogenic	0.7094	pathogenic	-1.103	Destabilizing	0.784	D	0.703	prob.neutral	None	None	None	None	N
H/W	0.7189	likely_pathogenic	0.6804	pathogenic	0.728	Stabilizing	0.989	D	0.692	prob.neutral	None	None	None	None	N
H/Y	0.1729	likely_benign	0.1618	benign	0.448	Stabilizing	0.002	N	0.375	neutral	N	0.468543919	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.