TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27004	81235;81236;81237	chr2:178565122;178565121;178565120	chr2:179429849;179429848;179429847
N2AB	25363	76312;76313;76314	chr2:178565122;178565121;178565120	chr2:179429849;179429848;179429847
N2A	24436	73531;73532;73533	chr2:178565122;178565121;178565120	chr2:179429849;179429848;179429847
N2B	17939	54040;54041;54042	chr2:178565122;178565121;178565120	chr2:179429849;179429848;179429847
Novex-1	18064	54415;54416;54417	chr2:178565122;178565121;178565120	chr2:179429849;179429848;179429847
Novex-2	18131	54616;54617;54618	chr2:178565122;178565121;178565120	chr2:179429849;179429848;179429847
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAA
• RefSeq wild type template codon: GTT
• Domain: Fn3-84
• Domain position: 33
• Structural Position: 34
• Q(SASA): 0.8153
• 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
Q/H	None	None	0.015	N	0.283	0.178	0.0884992946249	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	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
Q/A	0.1856	likely_benign	0.1755	benign	-0.118	Destabilizing	0.742	D	0.508	neutral	None	None	None	None	I
Q/C	0.7933	likely_pathogenic	0.7715	pathogenic	0.139	Stabilizing	0.996	D	0.563	neutral	None	None	None	None	I
Q/D	0.5466	ambiguous	0.5445	ambiguous	-0.034	Destabilizing	0.742	D	0.5	neutral	None	None	None	None	I
Q/E	0.1543	likely_benign	0.164	benign	-0.086	Destabilizing	0.472	N	0.475	neutral	N	0.42479785	None	None	I
Q/F	0.802	likely_pathogenic	0.774	pathogenic	-0.475	Destabilizing	0.953	D	0.547	neutral	None	None	None	None	I
Q/G	0.3934	ambiguous	0.3731	ambiguous	-0.249	Destabilizing	0.742	D	0.559	neutral	None	None	None	None	I
Q/H	0.303	likely_benign	0.2656	benign	-0.126	Destabilizing	0.015	N	0.283	neutral	N	0.520135027	None	None	I
Q/I	0.4305	ambiguous	0.4159	ambiguous	0.13	Stabilizing	0.953	D	0.561	neutral	None	None	None	None	I
Q/K	0.2599	likely_benign	0.2751	benign	0.117	Stabilizing	0.684	D	0.515	neutral	N	0.467839338	None	None	I
Q/L	0.185	likely_benign	0.1745	benign	0.13	Stabilizing	0.684	D	0.547	neutral	N	0.511496901	None	None	I
Q/M	0.3656	ambiguous	0.36	ambiguous	0.292	Stabilizing	0.984	D	0.464	neutral	None	None	None	None	I
Q/N	0.2845	likely_benign	0.2634	benign	-0.113	Destabilizing	0.742	D	0.477	neutral	None	None	None	None	I
Q/P	0.0887	likely_benign	0.0874	benign	0.072	Stabilizing	0.007	N	0.242	neutral	N	0.381719076	None	None	I
Q/R	0.2746	likely_benign	0.2882	benign	0.29	Stabilizing	0.684	D	0.529	neutral	N	0.488620042	None	None	I
Q/S	0.1945	likely_benign	0.1881	benign	-0.11	Destabilizing	0.742	D	0.509	neutral	None	None	None	None	I
Q/T	0.1987	likely_benign	0.1963	benign	-0.028	Destabilizing	0.742	D	0.526	neutral	None	None	None	None	I
Q/V	0.2517	likely_benign	0.2479	benign	0.072	Stabilizing	0.953	D	0.509	neutral	None	None	None	None	I
Q/W	0.8109	likely_pathogenic	0.8066	pathogenic	-0.512	Destabilizing	0.996	D	0.594	neutral	None	None	None	None	I
Q/Y	0.644	likely_pathogenic	0.6191	pathogenic	-0.228	Destabilizing	0.91	D	0.531	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.