TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26790	80593;80594;80595	chr2:178565764;178565763;178565762	chr2:179430491;179430490;179430489
N2AB	25149	75670;75671;75672	chr2:178565764;178565763;178565762	chr2:179430491;179430490;179430489
N2A	24222	72889;72890;72891	chr2:178565764;178565763;178565762	chr2:179430491;179430490;179430489
N2B	17725	53398;53399;53400	chr2:178565764;178565763;178565762	chr2:179430491;179430490;179430489
Novex-1	17850	53773;53774;53775	chr2:178565764;178565763;178565762	chr2:179430491;179430490;179430489
Novex-2	17917	53974;53975;53976	chr2:178565764;178565763;178565762	chr2:179430491;179430490;179430489
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: Fn3-83
• Domain position: 11
• Structural Position: 13
• Q(SASA): 0.344
• 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	rs1023059265	None	0.032	N	0.247	0.158	0.235664433957	gnomAD-4.0.0	1.59167E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85933E-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
T/A	0.1066	likely_benign	0.0988	benign	-0.653	Destabilizing	0.656	D	0.504	neutral	N	0.464937892	None	None	I
T/C	0.4077	ambiguous	0.4033	ambiguous	-0.302	Destabilizing	0.998	D	0.665	neutral	None	None	None	None	I
T/D	0.4977	ambiguous	0.4794	ambiguous	0.28	Stabilizing	0.993	D	0.674	neutral	None	None	None	None	I
T/E	0.3364	likely_benign	0.3353	benign	0.239	Stabilizing	0.993	D	0.607	neutral	None	None	None	None	I
T/F	0.2847	likely_benign	0.273	benign	-0.967	Destabilizing	0.956	D	0.725	prob.delet.	None	None	None	None	I
T/G	0.3058	likely_benign	0.2837	benign	-0.846	Destabilizing	0.978	D	0.623	neutral	None	None	None	None	I
T/H	0.3267	likely_benign	0.3145	benign	-1.105	Destabilizing	0.998	D	0.715	prob.delet.	None	None	None	None	I
T/I	0.1259	likely_benign	0.1414	benign	-0.25	Destabilizing	0.032	N	0.247	neutral	N	0.486409243	None	None	I
T/K	0.2164	likely_benign	0.2232	benign	-0.439	Destabilizing	0.978	D	0.608	neutral	None	None	None	None	I
T/L	0.0822	likely_benign	0.0883	benign	-0.25	Destabilizing	0.303	N	0.469	neutral	None	None	None	None	I
T/M	0.0773	likely_benign	0.078	benign	0.022	Stabilizing	0.559	D	0.367	neutral	None	None	None	None	I
T/N	0.1664	likely_benign	0.1599	benign	-0.259	Destabilizing	0.99	D	0.572	neutral	N	0.51673215	None	None	I
T/P	0.4755	ambiguous	0.3982	ambiguous	-0.354	Destabilizing	0.99	D	0.685	prob.neutral	N	0.486198265	None	None	I
T/Q	0.2403	likely_benign	0.235	benign	-0.452	Destabilizing	0.978	D	0.676	prob.neutral	None	None	None	None	I
T/R	0.1848	likely_benign	0.1851	benign	-0.192	Destabilizing	0.978	D	0.685	prob.neutral	None	None	None	None	I
T/S	0.1414	likely_benign	0.1317	benign	-0.566	Destabilizing	0.904	D	0.495	neutral	N	0.444943835	None	None	I
T/V	0.0996	likely_benign	0.1117	benign	-0.354	Destabilizing	0.303	N	0.501	neutral	None	None	None	None	I
T/W	0.6048	likely_pathogenic	0.5732	pathogenic	-0.908	Destabilizing	0.998	D	0.761	deleterious	None	None	None	None	I
T/Y	0.3421	ambiguous	0.3287	benign	-0.656	Destabilizing	0.978	D	0.733	prob.delet.	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.