TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26785	80578;80579;80580	chr2:178565779;178565778;178565777	chr2:179430506;179430505;179430504
N2AB	25144	75655;75656;75657	chr2:178565779;178565778;178565777	chr2:179430506;179430505;179430504
N2A	24217	72874;72875;72876	chr2:178565779;178565778;178565777	chr2:179430506;179430505;179430504
N2B	17720	53383;53384;53385	chr2:178565779;178565778;178565777	chr2:179430506;179430505;179430504
Novex-1	17845	53758;53759;53760	chr2:178565779;178565778;178565777	chr2:179430506;179430505;179430504
Novex-2	17912	53959;53960;53961	chr2:178565779;178565778;178565777	chr2:179430506;179430505;179430504
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Fn3-83
• Domain position: 6
• Structural Position: 6
• Q(SASA): 0.2227
• 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/A	None	None	0.996	N	0.692	0.395	0.284539287134	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
G/R	None	None	1.0	N	0.89	0.47	0.445007932271	gnomAD-4.0.0	4.10571E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.39745E-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
G/A	0.2035	likely_benign	0.1974	benign	-0.952	Destabilizing	0.996	D	0.692	prob.neutral	N	0.469647264	None	None	N
G/C	0.3774	ambiguous	0.3766	ambiguous	-1.148	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
G/D	0.6171	likely_pathogenic	0.6328	pathogenic	-2.243	Highly Destabilizing	0.999	D	0.817	deleterious	None	None	None	None	N
G/E	0.4605	ambiguous	0.4397	ambiguous	-2.213	Highly Destabilizing	0.96	D	0.647	neutral	N	0.517401366	None	None	N
G/F	0.7907	likely_pathogenic	0.776	pathogenic	-1.043	Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
G/H	0.6935	likely_pathogenic	0.6921	pathogenic	-1.89	Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	N
G/I	0.5494	ambiguous	0.5142	ambiguous	-0.29	Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
G/K	0.6126	likely_pathogenic	0.6049	pathogenic	-1.721	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
G/L	0.5807	likely_pathogenic	0.558	ambiguous	-0.29	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
G/M	0.6596	likely_pathogenic	0.6343	pathogenic	-0.267	Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
G/N	0.5616	ambiguous	0.5823	pathogenic	-1.56	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
G/P	0.9563	likely_pathogenic	0.956	pathogenic	-0.469	Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
G/Q	0.4888	ambiguous	0.4583	ambiguous	-1.631	Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
G/R	0.4549	ambiguous	0.4228	ambiguous	-1.47	Destabilizing	1.0	D	0.89	deleterious	N	0.518921519	None	None	N
G/S	0.1641	likely_benign	0.162	benign	-1.76	Destabilizing	0.999	D	0.797	deleterious	None	None	None	None	N
G/T	0.3524	ambiguous	0.3381	benign	-1.657	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
G/V	0.3855	ambiguous	0.3564	ambiguous	-0.469	Destabilizing	1.0	D	0.881	deleterious	N	0.481523776	None	None	N
G/W	0.7045	likely_pathogenic	0.686	pathogenic	-1.639	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
G/Y	0.7167	likely_pathogenic	0.7003	pathogenic	-1.181	Destabilizing	1.0	D	0.873	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.