TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20954	63085;63086;63087	chr2:178588865;178588864;178588863	chr2:179453592;179453591;179453590
N2AB	19313	58162;58163;58164	chr2:178588865;178588864;178588863	chr2:179453592;179453591;179453590
N2A	18386	55381;55382;55383	chr2:178588865;178588864;178588863	chr2:179453592;179453591;179453590
N2B	11889	35890;35891;35892	chr2:178588865;178588864;178588863	chr2:179453592;179453591;179453590
Novex-1	12014	36265;36266;36267	chr2:178588865;178588864;178588863	chr2:179453592;179453591;179453590
Novex-2	12081	36466;36467;36468	chr2:178588865;178588864;178588863	chr2:179453592;179453591;179453590
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-39
• Domain position: 91
• Structural Position: 126
• Q(SASA): 0.4701
• 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
P/Q	None	None	1.0	N	0.855	0.398	0.477219869099	gnomAD-4.0.0	6.84366E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.9957E-07	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
P/A	0.0677	likely_benign	0.0665	benign	-0.788	Destabilizing	0.999	D	0.796	deleterious	N	0.46355397	None	None	N
P/C	0.5619	ambiguous	0.45	ambiguous	-0.66	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
P/D	0.7974	likely_pathogenic	0.6784	pathogenic	-0.619	Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
P/E	0.5429	ambiguous	0.4179	ambiguous	-0.684	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
P/F	0.7312	likely_pathogenic	0.6342	pathogenic	-0.722	Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
P/G	0.3995	ambiguous	0.3453	ambiguous	-0.999	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
P/H	0.4195	ambiguous	0.3192	benign	-0.463	Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
P/I	0.4673	ambiguous	0.4031	ambiguous	-0.354	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
P/K	0.564	ambiguous	0.4168	ambiguous	-0.759	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
P/L	0.264	likely_benign	0.2117	benign	-0.354	Destabilizing	1.0	D	0.807	deleterious	N	0.498521486	None	None	N
P/M	0.4268	ambiguous	0.3668	ambiguous	-0.404	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
P/N	0.5617	ambiguous	0.4549	ambiguous	-0.517	Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	N
P/Q	0.3254	likely_benign	0.2595	benign	-0.723	Destabilizing	1.0	D	0.855	deleterious	N	0.511145239	None	None	N
P/R	0.4316	ambiguous	0.3004	benign	-0.207	Destabilizing	1.0	D	0.887	deleterious	N	0.488432628	None	None	N
P/S	0.1887	likely_benign	0.1574	benign	-0.914	Destabilizing	1.0	D	0.819	deleterious	N	0.508627168	None	None	N
P/T	0.1577	likely_benign	0.1333	benign	-0.875	Destabilizing	1.0	D	0.815	deleterious	N	0.504952144	None	None	N
P/V	0.2828	likely_benign	0.2463	benign	-0.463	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
P/W	0.8592	likely_pathogenic	0.7713	pathogenic	-0.844	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
P/Y	0.6989	likely_pathogenic	0.571	pathogenic	-0.557	Destabilizing	1.0	D	0.869	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.