TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34206	102841;102842;102843	chr2:178533999;178533998;178533997	chr2:179398726;179398725;179398724
N2AB	32565	97918;97919;97920	chr2:178533999;178533998;178533997	chr2:179398726;179398725;179398724
N2A	31638	95137;95138;95139	chr2:178533999;178533998;178533997	chr2:179398726;179398725;179398724
N2B	25141	75646;75647;75648	chr2:178533999;178533998;178533997	chr2:179398726;179398725;179398724
Novex-1	25266	76021;76022;76023	chr2:178533999;178533998;178533997	chr2:179398726;179398725;179398724
Novex-2	25333	76222;76223;76224	chr2:178533999;178533998;178533997	chr2:179398726;179398725;179398724
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-160
• Domain position: 70
• Structural Position: 153
• Q(SASA): 0.26
• 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
T/I	rs767516936	-0.362	0.051	N	0.279	0.153	0.350088858571	gnomAD-2.1.1	8.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	6.54E-05	None	0	0	0
T/I	rs767516936	-0.362	0.051	N	0.279	0.153	0.350088858571	gnomAD-4.0.0	1.59103E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43275E-05	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
T/A	0.2382	likely_benign	0.2577	benign	-1.227	Destabilizing	0.625	D	0.445	neutral	N	0.51479907	None	None	I
T/C	0.7492	likely_pathogenic	0.7885	pathogenic	-0.53	Destabilizing	0.998	D	0.539	neutral	None	None	None	None	I
T/D	0.8353	likely_pathogenic	0.8652	pathogenic	0.205	Stabilizing	0.842	D	0.533	neutral	None	None	None	None	I
T/E	0.7564	likely_pathogenic	0.7949	pathogenic	0.292	Stabilizing	0.842	D	0.489	neutral	None	None	None	None	I
T/F	0.6596	likely_pathogenic	0.6908	pathogenic	-1.185	Destabilizing	0.974	D	0.584	neutral	None	None	None	None	I
T/G	0.6762	likely_pathogenic	0.6962	pathogenic	-1.54	Destabilizing	0.842	D	0.533	neutral	None	None	None	None	I
T/H	0.6667	likely_pathogenic	0.7026	pathogenic	-1.527	Destabilizing	0.037	N	0.387	neutral	None	None	None	None	I
T/I	0.3404	ambiguous	0.3531	ambiguous	-0.449	Destabilizing	0.051	N	0.279	neutral	N	0.477800907	None	None	I
T/K	0.6143	likely_pathogenic	0.6406	pathogenic	-0.263	Destabilizing	0.842	D	0.495	neutral	None	None	None	None	I
T/L	0.2776	likely_benign	0.2897	benign	-0.449	Destabilizing	0.525	D	0.409	neutral	None	None	None	None	I
T/M	0.2316	likely_benign	0.2493	benign	-0.286	Destabilizing	0.974	D	0.561	neutral	None	None	None	None	I
T/N	0.358	ambiguous	0.4019	ambiguous	-0.429	Destabilizing	0.801	D	0.505	neutral	N	0.496560026	None	None	I
T/P	0.5012	ambiguous	0.5623	ambiguous	-0.678	Destabilizing	0.989	D	0.559	neutral	D	0.533827548	None	None	I
T/Q	0.597	likely_pathogenic	0.6332	pathogenic	-0.429	Destabilizing	0.949	D	0.569	neutral	None	None	None	None	I
T/R	0.5324	ambiguous	0.569	pathogenic	-0.226	Destabilizing	0.949	D	0.566	neutral	None	None	None	None	I
T/S	0.3285	likely_benign	0.3526	ambiguous	-0.903	Destabilizing	0.801	D	0.507	neutral	N	0.475664679	None	None	I
T/V	0.2878	likely_benign	0.3009	benign	-0.678	Destabilizing	0.029	N	0.17	neutral	None	None	None	None	I
T/W	0.89	likely_pathogenic	0.9023	pathogenic	-1.065	Destabilizing	0.998	D	0.608	neutral	None	None	None	None	I
T/Y	0.6483	likely_pathogenic	0.6831	pathogenic	-0.807	Destabilizing	0.949	D	0.587	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.