TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24378	73357;73358;73359	chr2:178573000;178572999;178572998	chr2:179437727;179437726;179437725
N2AB	22737	68434;68435;68436	chr2:178573000;178572999;178572998	chr2:179437727;179437726;179437725
N2A	21810	65653;65654;65655	chr2:178573000;178572999;178572998	chr2:179437727;179437726;179437725
N2B	15313	46162;46163;46164	chr2:178573000;178572999;178572998	chr2:179437727;179437726;179437725
Novex-1	15438	46537;46538;46539	chr2:178573000;178572999;178572998	chr2:179437727;179437726;179437725
Novex-2	15505	46738;46739;46740	chr2:178573000;178572999;178572998	chr2:179437727;179437726;179437725
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: Fn3-65
• Domain position: 56
• Structural Position: 75
• Q(SASA): 0.1998
• 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	0.991	N	0.633	0.266	0.168933306366	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
G/A	0.2088	likely_benign	0.1943	benign	-0.574	Destabilizing	0.991	D	0.633	neutral	N	0.491446916	None	None	N
G/C	0.3599	ambiguous	0.3287	benign	-0.74	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
G/D	0.7741	likely_pathogenic	0.6814	pathogenic	-0.988	Destabilizing	0.996	D	0.753	deleterious	None	None	None	None	N
G/E	0.6554	likely_pathogenic	0.5537	ambiguous	-1.108	Destabilizing	0.652	D	0.56	neutral	N	0.506261653	None	None	N
G/F	0.7703	likely_pathogenic	0.7259	pathogenic	-1.083	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
G/H	0.7389	likely_pathogenic	0.6802	pathogenic	-1.18	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
G/I	0.5133	ambiguous	0.4576	ambiguous	-0.417	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
G/K	0.754	likely_pathogenic	0.6899	pathogenic	-1.208	Destabilizing	0.996	D	0.791	deleterious	None	None	None	None	N
G/L	0.6228	likely_pathogenic	0.5848	pathogenic	-0.417	Destabilizing	0.998	D	0.849	deleterious	None	None	None	None	N
G/M	0.6483	likely_pathogenic	0.6118	pathogenic	-0.297	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
G/N	0.6392	likely_pathogenic	0.5779	pathogenic	-0.706	Destabilizing	0.998	D	0.763	deleterious	None	None	None	None	N
G/P	0.8806	likely_pathogenic	0.8559	pathogenic	-0.431	Destabilizing	0.999	D	0.831	deleterious	None	None	None	None	N
G/Q	0.642	likely_pathogenic	0.579	pathogenic	-0.962	Destabilizing	0.996	D	0.834	deleterious	None	None	None	None	N
G/R	0.6234	likely_pathogenic	0.5508	ambiguous	-0.824	Destabilizing	0.997	D	0.833	deleterious	N	0.485675737	None	None	N
G/S	0.2287	likely_benign	0.201	benign	-0.871	Destabilizing	0.998	D	0.737	prob.delet.	None	None	None	None	N
G/T	0.3777	ambiguous	0.3269	benign	-0.926	Destabilizing	0.998	D	0.806	deleterious	None	None	None	None	N
G/V	0.3941	ambiguous	0.3364	benign	-0.431	Destabilizing	0.999	D	0.845	deleterious	N	0.500335758	None	None	N
G/W	0.7178	likely_pathogenic	0.6542	pathogenic	-1.359	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
G/Y	0.6463	likely_pathogenic	0.6088	pathogenic	-0.995	Destabilizing	1.0	D	0.854	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.