TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29309	88150;88151;88152	chr2:178557337;178557336;178557335	chr2:179422064;179422063;179422062
N2AB	27668	83227;83228;83229	chr2:178557337;178557336;178557335	chr2:179422064;179422063;179422062
N2A	26741	80446;80447;80448	chr2:178557337;178557336;178557335	chr2:179422064;179422063;179422062
N2B	20244	60955;60956;60957	chr2:178557337;178557336;178557335	chr2:179422064;179422063;179422062
Novex-1	20369	61330;61331;61332	chr2:178557337;178557336;178557335	chr2:179422064;179422063;179422062
Novex-2	20436	61531;61532;61533	chr2:178557337;178557336;178557335	chr2:179422064;179422063;179422062
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-101
• Domain position: 73
• Structural Position: 105
• Q(SASA): 0.2082
• Predicted PPI site: I

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
E/G	rs1208405934	None	1.0	N	0.732	0.582	0.550005317886	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	1.92456E-04	None	0	0	0	0	0
E/G	rs1208405934	None	1.0	N	0.732	0.582	0.550005317886	gnomAD-4.0.0	6.5703E-06	None	None	None	None	I	None	0	0	None	0	1.92456E-04	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
E/A	0.6116	likely_pathogenic	0.6044	pathogenic	-1.506	Destabilizing	0.999	D	0.659	neutral	N	0.499085053	None	None	I
E/C	0.9569	likely_pathogenic	0.9521	pathogenic	-0.776	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	I
E/D	0.7474	likely_pathogenic	0.8311	pathogenic	-1.777	Destabilizing	0.999	D	0.511	neutral	N	0.507580976	None	None	I
E/F	0.9819	likely_pathogenic	0.9837	pathogenic	-1.126	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	I
E/G	0.8204	likely_pathogenic	0.8244	pathogenic	-1.928	Destabilizing	1.0	D	0.732	prob.delet.	N	0.516228256	None	None	I
E/H	0.9361	likely_pathogenic	0.9409	pathogenic	-1.119	Destabilizing	1.0	D	0.675	neutral	None	None	None	None	I
E/I	0.831	likely_pathogenic	0.887	pathogenic	-0.29	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	I
E/K	0.8535	likely_pathogenic	0.8551	pathogenic	-1.542	Destabilizing	0.999	D	0.591	neutral	N	0.471648727	None	None	I
E/L	0.9115	likely_pathogenic	0.9378	pathogenic	-0.29	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	I
E/M	0.8569	likely_pathogenic	0.8698	pathogenic	0.484	Stabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	I
E/N	0.8873	likely_pathogenic	0.9024	pathogenic	-1.862	Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	I
E/P	0.999	likely_pathogenic	0.9993	pathogenic	-0.681	Destabilizing	1.0	D	0.744	deleterious	None	None	None	None	I
E/Q	0.3765	ambiguous	0.3401	ambiguous	-1.516	Destabilizing	1.0	D	0.651	neutral	N	0.501685339	None	None	I
E/R	0.8973	likely_pathogenic	0.8917	pathogenic	-1.404	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	I
E/S	0.6582	likely_pathogenic	0.6457	pathogenic	-2.506	Highly Destabilizing	0.999	D	0.635	neutral	None	None	None	None	I
E/T	0.7185	likely_pathogenic	0.7496	pathogenic	-2.101	Highly Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	I
E/V	0.6898	likely_pathogenic	0.7639	pathogenic	-0.681	Destabilizing	1.0	D	0.737	prob.delet.	N	0.476839741	None	None	I
E/W	0.9962	likely_pathogenic	0.9966	pathogenic	-1.209	Destabilizing	1.0	D	0.782	deleterious	None	None	None	None	I
E/Y	0.9714	likely_pathogenic	0.9728	pathogenic	-0.952	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	I

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.