TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25348	76267;76268;76269	chr2:178570090;178570089;178570088	chr2:179434817;179434816;179434815
N2AB	23707	71344;71345;71346	chr2:178570090;178570089;178570088	chr2:179434817;179434816;179434815
N2A	22780	68563;68564;68565	chr2:178570090;178570089;178570088	chr2:179434817;179434816;179434815
N2B	16283	49072;49073;49074	chr2:178570090;178570089;178570088	chr2:179434817;179434816;179434815
Novex-1	16408	49447;49448;49449	chr2:178570090;178570089;178570088	chr2:179434817;179434816;179434815
Novex-2	16475	49648;49649;49650	chr2:178570090;178570089;178570088	chr2:179434817;179434816;179434815
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Fn3-72
• Domain position: 45
• Structural Position: 60
• Q(SASA): 0.346
• 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
G/D	None	None	0.988	N	0.589	0.403	0.338834610459	gnomAD-4.0.0	6.84352E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99598E-07	0	0
G/V	None	None	0.988	N	0.683	0.438	0.495372917472	gnomAD-4.0.0	6.84352E-07	None	None	None	None	N	None	0	0	None	0	0	None	1.87413E-05	0	0	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
G/A	0.295	likely_benign	0.2684	benign	-0.445	Destabilizing	0.919	D	0.456	neutral	N	0.466503258	None	None	N
G/C	0.5413	ambiguous	0.5346	ambiguous	-0.905	Destabilizing	0.999	D	0.739	prob.delet.	N	0.504486195	None	None	N
G/D	0.8307	likely_pathogenic	0.8165	pathogenic	-0.83	Destabilizing	0.988	D	0.589	neutral	N	0.508259021	None	None	N
G/E	0.8539	likely_pathogenic	0.8345	pathogenic	-0.995	Destabilizing	0.991	D	0.631	neutral	None	None	None	None	N
G/F	0.9366	likely_pathogenic	0.9283	pathogenic	-1.128	Destabilizing	0.999	D	0.737	prob.delet.	None	None	None	None	N
G/H	0.8972	likely_pathogenic	0.8816	pathogenic	-0.673	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
G/I	0.8038	likely_pathogenic	0.7851	pathogenic	-0.562	Destabilizing	0.999	D	0.732	prob.delet.	None	None	None	None	N
G/K	0.9495	likely_pathogenic	0.9436	pathogenic	-1.027	Destabilizing	0.991	D	0.627	neutral	None	None	None	None	N
G/L	0.858	likely_pathogenic	0.8395	pathogenic	-0.562	Destabilizing	0.991	D	0.677	prob.neutral	None	None	None	None	N
G/M	0.8353	likely_pathogenic	0.8148	pathogenic	-0.542	Destabilizing	1.0	D	0.734	prob.delet.	None	None	None	None	N
G/N	0.6448	likely_pathogenic	0.6042	pathogenic	-0.617	Destabilizing	0.991	D	0.634	neutral	None	None	None	None	N
G/P	0.995	likely_pathogenic	0.9948	pathogenic	-0.49	Destabilizing	0.995	D	0.667	neutral	None	None	None	None	N
G/Q	0.8778	likely_pathogenic	0.8627	pathogenic	-0.933	Destabilizing	0.991	D	0.693	prob.neutral	None	None	None	None	N
G/R	0.9031	likely_pathogenic	0.8958	pathogenic	-0.506	Destabilizing	0.988	D	0.677	prob.neutral	N	0.520305599	None	None	N
G/S	0.197	likely_benign	0.1687	benign	-0.742	Destabilizing	0.234	N	0.43	neutral	N	0.443380823	None	None	N
G/T	0.4761	ambiguous	0.4296	ambiguous	-0.845	Destabilizing	0.982	D	0.627	neutral	None	None	None	None	N
G/V	0.6454	likely_pathogenic	0.6201	pathogenic	-0.49	Destabilizing	0.988	D	0.683	prob.neutral	N	0.47658257	None	None	N
G/W	0.895	likely_pathogenic	0.8875	pathogenic	-1.267	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
G/Y	0.8754	likely_pathogenic	0.8613	pathogenic	-0.946	Destabilizing	1.0	D	0.741	deleterious	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.