TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18113	54562;54563;54564	chr2:178604752;178604751;178604750	chr2:179469479;179469478;179469477
N2AB	16472	49639;49640;49641	chr2:178604752;178604751;178604750	chr2:179469479;179469478;179469477
N2A	15545	46858;46859;46860	chr2:178604752;178604751;178604750	chr2:179469479;179469478;179469477
N2B	9048	27367;27368;27369	chr2:178604752;178604751;178604750	chr2:179469479;179469478;179469477
Novex-1	9173	27742;27743;27744	chr2:178604752;178604751;178604750	chr2:179469479;179469478;179469477
Novex-2	9240	27943;27944;27945	chr2:178604752;178604751;178604750	chr2:179469479;179469478;179469477
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-19
• Domain position: 49
• Structural Position: 64
• Q(SASA): 0.6167
• 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
E/K	None	None	0.698	N	0.487	0.231	0.347438807231	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
E/A	0.1469	likely_benign	0.1275	benign	-0.086	Destabilizing	0.822	D	0.441	neutral	N	0.466897975	None	None	N
E/C	0.8507	likely_pathogenic	0.7855	pathogenic	-0.371	Destabilizing	0.998	D	0.635	neutral	None	None	None	None	N
E/D	0.0847	likely_benign	0.0849	benign	-0.209	Destabilizing	0.014	N	0.265	neutral	N	0.425475427	None	None	N
E/F	0.7589	likely_pathogenic	0.6878	pathogenic	-0.083	Destabilizing	0.998	D	0.543	neutral	None	None	None	None	N
E/G	0.1898	likely_benign	0.164	benign	-0.205	Destabilizing	0.822	D	0.419	neutral	N	0.446658776	None	None	N
E/H	0.5478	ambiguous	0.4427	ambiguous	0.601	Stabilizing	0.978	D	0.389	neutral	None	None	None	None	N
E/I	0.3272	likely_benign	0.2629	benign	0.176	Stabilizing	0.978	D	0.551	neutral	None	None	None	None	N
E/K	0.2371	likely_benign	0.178	benign	0.239	Stabilizing	0.698	D	0.487	neutral	N	0.439943447	None	None	N
E/L	0.3704	ambiguous	0.3012	benign	0.176	Stabilizing	0.956	D	0.53	neutral	None	None	None	None	N
E/M	0.4934	ambiguous	0.4183	ambiguous	-0.139	Destabilizing	0.998	D	0.509	neutral	None	None	None	None	N
E/N	0.2045	likely_benign	0.1859	benign	0.053	Stabilizing	0.915	D	0.387	neutral	None	None	None	None	N
E/P	0.3413	ambiguous	0.3112	benign	0.106	Stabilizing	0.978	D	0.399	neutral	None	None	None	None	N
E/Q	0.1838	likely_benign	0.1412	benign	0.066	Stabilizing	0.153	N	0.265	neutral	N	0.462820307	None	None	N
E/R	0.4134	ambiguous	0.3115	benign	0.563	Stabilizing	0.956	D	0.39	neutral	None	None	None	None	N
E/S	0.1814	likely_benign	0.1645	benign	-0.137	Destabilizing	0.86	D	0.451	neutral	None	None	None	None	N
E/T	0.2027	likely_benign	0.1796	benign	-0.032	Destabilizing	0.956	D	0.363	neutral	None	None	None	None	N
E/V	0.2067	likely_benign	0.1646	benign	0.106	Stabilizing	0.971	D	0.471	neutral	N	0.457835775	None	None	N
E/W	0.9158	likely_pathogenic	0.867	pathogenic	-0.021	Destabilizing	0.998	D	0.646	neutral	None	None	None	None	N
E/Y	0.658	likely_pathogenic	0.5708	pathogenic	0.14	Stabilizing	0.993	D	0.488	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.