TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32388	97387;97388;97389	chr2:178542692;178542691;178542690	chr2:179407419;179407418;179407417
N2AB	30747	92464;92465;92466	chr2:178542692;178542691;178542690	chr2:179407419;179407418;179407417
N2A	29820	89683;89684;89685	chr2:178542692;178542691;178542690	chr2:179407419;179407418;179407417
N2B	23323	70192;70193;70194	chr2:178542692;178542691;178542690	chr2:179407419;179407418;179407417
Novex-1	23448	70567;70568;70569	chr2:178542692;178542691;178542690	chr2:179407419;179407418;179407417
Novex-2	23515	70768;70769;70770	chr2:178542692;178542691;178542690	chr2:179407419;179407418;179407417
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-154
• Domain position: 82
• Structural Position: 166
• Q(SASA): 0.2997
• 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
T/N	None	None	0.966	N	0.435	0.193	0.234412748748	gnomAD-4.0.0	1.59164E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02444E-05

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	0.0595	likely_benign	0.058	benign	-0.238	Destabilizing	0.002	N	0.125	neutral	N	0.386249743	None	None	N
T/C	0.3103	likely_benign	0.2792	benign	-0.24	Destabilizing	0.993	D	0.456	neutral	None	None	None	None	N
T/D	0.3675	ambiguous	0.3179	benign	0.132	Stabilizing	0.974	D	0.446	neutral	None	None	None	None	N
T/E	0.3153	likely_benign	0.2827	benign	0.044	Stabilizing	0.842	D	0.446	neutral	None	None	None	None	N
T/F	0.2475	likely_benign	0.1984	benign	-0.822	Destabilizing	0.974	D	0.566	neutral	None	None	None	None	N
T/G	0.2181	likely_benign	0.1943	benign	-0.335	Destabilizing	0.728	D	0.502	neutral	None	None	None	None	N
T/H	0.2648	likely_benign	0.2244	benign	-0.619	Destabilizing	0.998	D	0.544	neutral	None	None	None	None	N
T/I	0.1163	likely_benign	0.1016	benign	-0.109	Destabilizing	0.669	D	0.409	neutral	N	0.419690313	None	None	N
T/K	0.1982	likely_benign	0.1755	benign	-0.276	Destabilizing	0.842	D	0.447	neutral	None	None	None	None	N
T/L	0.1027	likely_benign	0.0868	benign	-0.109	Destabilizing	0.525	D	0.407	neutral	None	None	None	None	N
T/M	0.0969	likely_benign	0.0925	benign	0.001	Stabilizing	0.974	D	0.463	neutral	None	None	None	None	N
T/N	0.1485	likely_benign	0.1268	benign	-0.047	Destabilizing	0.966	D	0.435	neutral	N	0.465345245	None	None	N
T/P	0.6511	likely_pathogenic	0.5715	pathogenic	-0.125	Destabilizing	0.966	D	0.449	neutral	N	0.451916225	None	None	N
T/Q	0.2233	likely_benign	0.2046	benign	-0.28	Destabilizing	0.974	D	0.465	neutral	None	None	None	None	N
T/R	0.1614	likely_benign	0.1375	benign	-0.01	Destabilizing	0.974	D	0.457	neutral	None	None	None	None	N
T/S	0.1067	likely_benign	0.095	benign	-0.228	Destabilizing	0.454	N	0.395	neutral	N	0.454735889	None	None	N
T/V	0.0935	likely_benign	0.0845	benign	-0.125	Destabilizing	0.007	N	0.118	neutral	None	None	None	None	N
T/W	0.6827	likely_pathogenic	0.6345	pathogenic	-0.863	Destabilizing	0.998	D	0.593	neutral	None	None	None	None	N
T/Y	0.2952	likely_benign	0.2578	benign	-0.556	Destabilizing	0.991	D	0.565	neutral	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.