TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31588	94987;94988;94989	chr2:178546666;178546665;178546664	chr2:179411393;179411392;179411391
N2AB	29947	90064;90065;90066	chr2:178546666;178546665;178546664	chr2:179411393;179411392;179411391
N2A	29020	87283;87284;87285	chr2:178546666;178546665;178546664	chr2:179411393;179411392;179411391
N2B	22523	67792;67793;67794	chr2:178546666;178546665;178546664	chr2:179411393;179411392;179411391
Novex-1	22648	68167;68168;68169	chr2:178546666;178546665;178546664	chr2:179411393;179411392;179411391
Novex-2	22715	68368;68369;68370	chr2:178546666;178546665;178546664	chr2:179411393;179411392;179411391
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-118
• Domain position: 83
• Structural Position: 112
• Q(SASA): 0.1226
• 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
N/K	None	None	1.0	D	0.753	0.471	0.294561560033	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
N/A	0.9986	likely_pathogenic	0.9984	pathogenic	-0.446	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
N/C	0.9909	likely_pathogenic	0.9901	pathogenic	-0.424	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
N/D	0.9828	likely_pathogenic	0.977	pathogenic	-2.126	Highly Destabilizing	0.999	D	0.62	neutral	N	0.51479036	None	None	N
N/E	0.9993	likely_pathogenic	0.9993	pathogenic	-1.992	Destabilizing	0.999	D	0.723	prob.delet.	None	None	None	None	N
N/F	0.9998	likely_pathogenic	0.9997	pathogenic	-0.533	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
N/G	0.9953	likely_pathogenic	0.9945	pathogenic	-0.736	Destabilizing	0.999	D	0.589	neutral	None	None	None	None	N
N/H	0.992	likely_pathogenic	0.99	pathogenic	-0.565	Destabilizing	1.0	D	0.79	deleterious	D	0.569560878	None	None	N
N/I	0.9967	likely_pathogenic	0.9966	pathogenic	0.275	Stabilizing	1.0	D	0.835	deleterious	D	0.558293478	None	None	N
N/K	0.9993	likely_pathogenic	0.9991	pathogenic	-0.099	Destabilizing	1.0	D	0.753	deleterious	D	0.56854692	None	None	N
N/L	0.9926	likely_pathogenic	0.9923	pathogenic	0.275	Stabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
N/M	0.9948	likely_pathogenic	0.9941	pathogenic	0.549	Stabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
N/P	0.9993	likely_pathogenic	0.9992	pathogenic	0.063	Stabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
N/Q	0.9994	likely_pathogenic	0.9992	pathogenic	-1.112	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
N/R	0.9991	likely_pathogenic	0.9991	pathogenic	-0.023	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
N/S	0.9384	likely_pathogenic	0.9256	pathogenic	-0.881	Destabilizing	0.999	D	0.615	neutral	N	0.521018104	None	None	N
N/T	0.9341	likely_pathogenic	0.9261	pathogenic	-0.598	Destabilizing	0.999	D	0.714	prob.delet.	N	0.504164389	None	None	N
N/V	0.995	likely_pathogenic	0.9953	pathogenic	0.063	Stabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
N/W	0.9999	likely_pathogenic	0.9999	pathogenic	-0.536	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
N/Y	0.9969	likely_pathogenic	0.9962	pathogenic	-0.079	Destabilizing	1.0	D	0.843	deleterious	D	0.569560878	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.