TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9711	29356;29357;29358	chr2:178706865;178706864;178706863	chr2:179571592;179571591;179571590
N2AB	9394	28405;28406;28407	chr2:178706865;178706864;178706863	chr2:179571592;179571591;179571590
N2A	8467	25624;25625;25626	chr2:178706865;178706864;178706863	chr2:179571592;179571591;179571590
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-83
• Domain position: 14
• Structural Position: 23
• Q(SASA): 0.3317
• 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/Q	rs2075957760	None	0.999	None	0.579	0.304	0.234412748748	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
E/Q	rs2075957760	None	0.999	None	0.579	0.304	0.234412748748	gnomAD-4.0.0	2.02989E-06	None	None	None	None	I	None	0	6.15006E-05	None	0	0	None	0	0	1.20494E-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
E/A	0.7913	likely_pathogenic	0.5797	pathogenic	-0.866	Destabilizing	0.998	D	0.517	neutral	None	None	None	None	I
E/C	0.9951	likely_pathogenic	0.9884	pathogenic	-0.313	Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	I
E/D	0.8962	likely_pathogenic	0.7276	pathogenic	-0.968	Destabilizing	0.998	D	0.358	neutral	None	None	None	None	I
E/F	0.9976	likely_pathogenic	0.9892	pathogenic	-0.697	Destabilizing	1.0	D	0.756	deleterious	None	None	None	None	I
E/G	0.8054	likely_pathogenic	0.5484	ambiguous	-1.159	Destabilizing	0.999	D	0.6	neutral	None	None	None	None	I
E/H	0.9893	likely_pathogenic	0.9596	pathogenic	-0.908	Destabilizing	0.702	D	0.368	neutral	None	None	None	None	I
E/I	0.9852	likely_pathogenic	0.9406	pathogenic	-0.086	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	I
E/K	0.9105	likely_pathogenic	0.7003	pathogenic	-0.333	Destabilizing	0.998	D	0.465	neutral	None	None	None	None	I
E/L	0.9814	likely_pathogenic	0.9267	pathogenic	-0.086	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	I
E/M	0.9833	likely_pathogenic	0.9342	pathogenic	0.359	Stabilizing	1.0	D	0.682	prob.neutral	None	None	None	None	I
E/N	0.9654	likely_pathogenic	0.8816	pathogenic	-0.697	Destabilizing	0.999	D	0.595	neutral	None	None	None	None	I
E/P	0.9782	likely_pathogenic	0.9331	pathogenic	-0.326	Destabilizing	1.0	D	0.616	neutral	None	None	None	None	I
E/Q	0.7184	likely_pathogenic	0.4909	ambiguous	-0.64	Destabilizing	0.999	D	0.579	neutral	None	None	None	None	I
E/R	0.94	likely_pathogenic	0.8098	pathogenic	-0.185	Destabilizing	1.0	D	0.61	neutral	None	None	None	None	I
E/S	0.8825	likely_pathogenic	0.7116	pathogenic	-0.954	Destabilizing	0.998	D	0.517	neutral	None	None	None	None	I
E/T	0.9477	likely_pathogenic	0.829	pathogenic	-0.713	Destabilizing	1.0	D	0.591	neutral	None	None	None	None	I
E/V	0.9538	likely_pathogenic	0.8464	pathogenic	-0.326	Destabilizing	1.0	D	0.678	prob.neutral	None	None	None	None	I
E/W	0.9988	likely_pathogenic	0.9945	pathogenic	-0.512	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	I
E/Y	0.9952	likely_pathogenic	0.9804	pathogenic	-0.451	Destabilizing	0.999	D	0.693	prob.neutral	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.