TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8090	24493;24494;24495	chr2:178718932;178718931;178718930	chr2:179583659;179583658;179583657
N2AB	7773	23542;23543;23544	chr2:178718932;178718931;178718930	chr2:179583659;179583658;179583657
N2A	6846	20761;20762;20763	chr2:178718932;178718931;178718930	chr2:179583659;179583658;179583657
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: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Ig-66
• Domain position: 13
• Structural Position: 18
• Q(SASA): 0.6893
• 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
L/F	None	None	0.989	N	0.447	0.296	0.568036332872	gnomAD-4.0.0	6.85156E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.00213E-07	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
L/A	0.2991	likely_benign	0.2445	benign	-0.869	Destabilizing	0.97	D	0.525	neutral	None	None	None	None	I
L/C	0.6997	likely_pathogenic	0.561	ambiguous	-0.709	Destabilizing	1.0	D	0.542	neutral	None	None	None	None	I
L/D	0.6565	likely_pathogenic	0.5914	pathogenic	-0.537	Destabilizing	0.996	D	0.649	neutral	None	None	None	None	I
L/E	0.3523	ambiguous	0.2982	benign	-0.595	Destabilizing	0.996	D	0.65	neutral	None	None	None	None	I
L/F	0.1605	likely_benign	0.125	benign	-0.685	Destabilizing	0.989	D	0.447	neutral	N	0.518066633	None	None	I
L/G	0.5965	likely_pathogenic	0.5203	ambiguous	-1.08	Destabilizing	0.996	D	0.641	neutral	None	None	None	None	I
L/H	0.2842	likely_benign	0.2246	benign	-0.243	Destabilizing	1.0	D	0.68	prob.neutral	None	None	None	None	I
L/I	0.1137	likely_benign	0.101	benign	-0.411	Destabilizing	0.304	N	0.274	neutral	None	None	None	None	I
L/K	0.2879	likely_benign	0.2492	benign	-0.636	Destabilizing	0.996	D	0.611	neutral	None	None	None	None	I
L/M	0.137	likely_benign	0.1219	benign	-0.505	Destabilizing	0.835	D	0.439	neutral	D	0.533635547	None	None	I
L/N	0.4006	ambiguous	0.3386	benign	-0.479	Destabilizing	0.996	D	0.649	neutral	None	None	None	None	I
L/P	0.3185	likely_benign	0.2769	benign	-0.531	Destabilizing	0.999	D	0.649	neutral	None	None	None	None	I
L/Q	0.1861	likely_benign	0.1483	benign	-0.679	Destabilizing	0.996	D	0.627	neutral	None	None	None	None	I
L/R	0.2322	likely_benign	0.1963	benign	-0.033	Destabilizing	0.996	D	0.622	neutral	None	None	None	None	I
L/S	0.2789	likely_benign	0.2078	benign	-0.93	Destabilizing	0.977	D	0.557	neutral	N	0.490119647	None	None	I
L/T	0.2515	likely_benign	0.2085	benign	-0.878	Destabilizing	0.503	D	0.339	neutral	None	None	None	None	I
L/V	0.122	likely_benign	0.1076	benign	-0.531	Destabilizing	0.248	N	0.303	neutral	N	0.510932046	None	None	I
L/W	0.3433	ambiguous	0.269	benign	-0.72	Destabilizing	1.0	D	0.699	prob.neutral	N	0.518320122	None	None	I
L/Y	0.3907	ambiguous	0.3177	benign	-0.49	Destabilizing	0.999	D	0.492	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.