TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15780	47563;47564;47565	chr2:178618013;178618012;178618011	chr2:179482740;179482739;179482738
N2AB	14139	42640;42641;42642	chr2:178618013;178618012;178618011	chr2:179482740;179482739;179482738
N2A	13212	39859;39860;39861	chr2:178618013;178618012;178618011	chr2:179482740;179482739;179482738
N2B	6715	20368;20369;20370	chr2:178618013;178618012;178618011	chr2:179482740;179482739;179482738
Novex-1	6840	20743;20744;20745	chr2:178618013;178618012;178618011	chr2:179482740;179482739;179482738
Novex-2	6907	20944;20945;20946	chr2:178618013;178618012;178618011	chr2:179482740;179482739;179482738
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: Fn3-2
• Domain position: 23
• Structural Position: 25
• Q(SASA): 0.4041
• 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/D	None	None	0.434	N	0.263	0.051	0.232513804876	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.1804	likely_benign	0.1668	benign	-0.771	Destabilizing	0.998	D	0.677	prob.neutral	N	0.483114705	None	None	N
E/C	0.8204	likely_pathogenic	0.7793	pathogenic	-0.468	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
E/D	0.1832	likely_benign	0.1716	benign	-1.122	Destabilizing	0.434	N	0.263	neutral	N	0.482863495	None	None	N
E/F	0.7129	likely_pathogenic	0.6707	pathogenic	-0.128	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
E/G	0.2136	likely_benign	0.2039	benign	-1.145	Destabilizing	0.999	D	0.756	deleterious	N	0.478406358	None	None	N
E/H	0.4725	ambiguous	0.4355	ambiguous	-0.32	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	N
E/I	0.3146	likely_benign	0.2823	benign	0.25	Stabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
E/K	0.1592	likely_benign	0.1541	benign	-0.636	Destabilizing	0.998	D	0.536	neutral	N	0.439557344	None	None	N
E/L	0.3347	likely_benign	0.3063	benign	0.25	Stabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
E/M	0.364	ambiguous	0.3378	benign	0.627	Stabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
E/N	0.2431	likely_benign	0.227	benign	-1.164	Destabilizing	0.999	D	0.699	prob.neutral	None	None	None	None	N
E/P	0.9558	likely_pathogenic	0.9495	pathogenic	-0.068	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
E/Q	0.117	likely_benign	0.1145	benign	-1.002	Destabilizing	0.999	D	0.657	neutral	N	0.483310471	None	None	N
E/R	0.2748	likely_benign	0.2569	benign	-0.279	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
E/S	0.2057	likely_benign	0.1859	benign	-1.452	Destabilizing	0.997	D	0.586	neutral	None	None	None	None	N
E/T	0.2048	likely_benign	0.1856	benign	-1.142	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
E/V	0.2027	likely_benign	0.1832	benign	-0.068	Destabilizing	1.0	D	0.795	deleterious	N	0.48218607	None	None	N
E/W	0.9066	likely_pathogenic	0.8847	pathogenic	0.122	Stabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
E/Y	0.6182	likely_pathogenic	0.5735	pathogenic	0.116	Stabilizing	1.0	D	0.817	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.