TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35456	106591;106592;106593	chr2:178530249;178530248;178530247	chr2:179394976;179394975;179394974
N2AB	33815	101668;101669;101670	chr2:178530249;178530248;178530247	chr2:179394976;179394975;179394974
N2A	32888	98887;98888;98889	chr2:178530249;178530248;178530247	chr2:179394976;179394975;179394974
N2B	26391	79396;79397;79398	chr2:178530249;178530248;178530247	chr2:179394976;179394975;179394974
Novex-1	26516	79771;79772;79773	chr2:178530249;178530248;178530247	chr2:179394976;179394975;179394974
Novex-2	26583	79972;79973;79974	chr2:178530249;178530248;178530247	chr2:179394976;179394975;179394974
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-166
• Domain position: 37
• Structural Position: 51
• Q(SASA): 0.2601
• 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
D/V	rs1288351302	-0.056	1.0	N	0.673	0.495	0.516326692288	gnomAD-4.0.0	1.64028E-06	None	None	None	None	N	None	0	2.48188E-05	None	0	0	None	0	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
D/A	0.3994	ambiguous	0.3948	ambiguous	-0.618	Destabilizing	0.995	D	0.557	neutral	N	0.478981518	None	None	N
D/C	0.8913	likely_pathogenic	0.8834	pathogenic	-0.234	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
D/E	0.3836	ambiguous	0.3731	ambiguous	-0.302	Destabilizing	0.99	D	0.479	neutral	N	0.456798659	None	None	N
D/F	0.8434	likely_pathogenic	0.8489	pathogenic	-0.185	Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	N
D/G	0.2275	likely_benign	0.2216	benign	-0.882	Destabilizing	0.99	D	0.567	neutral	N	0.457897841	None	None	N
D/H	0.6414	likely_pathogenic	0.6399	pathogenic	-0.109	Destabilizing	1.0	D	0.6	neutral	N	0.503682365	None	None	N
D/I	0.8215	likely_pathogenic	0.8291	pathogenic	0.058	Stabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
D/K	0.7478	likely_pathogenic	0.7354	pathogenic	0.045	Stabilizing	0.998	D	0.574	neutral	None	None	None	None	N
D/L	0.7717	likely_pathogenic	0.7752	pathogenic	0.058	Stabilizing	0.999	D	0.68	prob.neutral	None	None	None	None	N
D/M	0.8979	likely_pathogenic	0.9024	pathogenic	0.282	Stabilizing	1.0	D	0.674	neutral	None	None	None	None	N
D/N	0.1407	likely_benign	0.1267	benign	-0.472	Destabilizing	0.561	D	0.367	neutral	N	0.475351595	None	None	N
D/P	0.9771	likely_pathogenic	0.982	pathogenic	-0.145	Destabilizing	1.0	D	0.599	neutral	None	None	None	None	N
D/Q	0.7067	likely_pathogenic	0.6915	pathogenic	-0.374	Destabilizing	0.999	D	0.579	neutral	None	None	None	None	N
D/R	0.7529	likely_pathogenic	0.7469	pathogenic	0.3	Stabilizing	0.999	D	0.613	neutral	None	None	None	None	N
D/S	0.2757	likely_benign	0.2569	benign	-0.614	Destabilizing	0.992	D	0.527	neutral	None	None	None	None	N
D/T	0.6637	likely_pathogenic	0.6617	pathogenic	-0.389	Destabilizing	0.992	D	0.583	neutral	None	None	None	None	N
D/V	0.6146	likely_pathogenic	0.6328	pathogenic	-0.145	Destabilizing	1.0	D	0.673	neutral	N	0.487806609	None	None	N
D/W	0.9509	likely_pathogenic	0.9544	pathogenic	0.093	Stabilizing	1.0	D	0.708	prob.delet.	None	None	None	None	N
D/Y	0.3713	ambiguous	0.3887	ambiguous	0.08	Stabilizing	1.0	D	0.677	prob.neutral	N	0.503935855	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.