TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5939	18040;18041;18042	chr2:178730718;178730717;178730716	chr2:179595445;179595444;179595443
N2AB	5622	17089;17090;17091	chr2:178730718;178730717;178730716	chr2:179595445;179595444;179595443
N2A	4695	14308;14309;14310	chr2:178730718;178730717;178730716	chr2:179595445;179595444;179595443
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-43
• Domain position: 21
• Structural Position: 31
• Q(SASA): 0.4443
• 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/G	None	None	0.999	D	0.718	0.675	0.751210634423	gnomAD-4.0.0	1.59203E-06	None	None	None	None	N	None	0	2.28749E-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	0.491	ambiguous	0.4715	ambiguous	-0.842	Destabilizing	0.998	D	0.639	neutral	N	0.502052746	None	None	N
E/C	0.981	likely_pathogenic	0.9807	pathogenic	-0.482	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
E/D	0.7115	likely_pathogenic	0.6983	pathogenic	-1.214	Destabilizing	0.434	N	0.283	neutral	N	0.502795352	None	None	N
E/F	0.9807	likely_pathogenic	0.9781	pathogenic	-0.044	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
E/G	0.6716	likely_pathogenic	0.6626	pathogenic	-1.259	Destabilizing	0.999	D	0.718	prob.delet.	D	0.522665443	None	None	N
E/H	0.877	likely_pathogenic	0.8719	pathogenic	-0.311	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
E/I	0.8882	likely_pathogenic	0.8725	pathogenic	0.315	Stabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
E/K	0.6405	likely_pathogenic	0.6507	pathogenic	-0.727	Destabilizing	0.998	D	0.527	neutral	N	0.485897047	None	None	N
E/L	0.9044	likely_pathogenic	0.8928	pathogenic	0.315	Stabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
E/M	0.8995	likely_pathogenic	0.8882	pathogenic	0.802	Stabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
E/N	0.8292	likely_pathogenic	0.8118	pathogenic	-1.308	Destabilizing	0.999	D	0.707	prob.neutral	None	None	None	None	N
E/P	0.982	likely_pathogenic	0.9821	pathogenic	-0.049	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
E/Q	0.319	likely_benign	0.3207	benign	-1.118	Destabilizing	0.999	D	0.662	neutral	N	0.491999887	None	None	N
E/R	0.7254	likely_pathogenic	0.7382	pathogenic	-0.387	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
E/S	0.607	likely_pathogenic	0.594	pathogenic	-1.673	Destabilizing	0.997	D	0.574	neutral	None	None	None	None	N
E/T	0.6852	likely_pathogenic	0.6678	pathogenic	-1.318	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
E/V	0.7012	likely_pathogenic	0.6731	pathogenic	-0.049	Destabilizing	1.0	D	0.761	deleterious	N	0.505802182	None	None	N
E/W	0.9938	likely_pathogenic	0.9933	pathogenic	0.239	Stabilizing	1.0	D	0.768	deleterious	None	None	None	None	N
E/Y	0.9633	likely_pathogenic	0.9595	pathogenic	0.223	Stabilizing	1.0	D	0.783	deleterious	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.