TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6688	20287;20288;20289	chr2:178727303;178727302;178727301	chr2:179592030;179592029;179592028
N2AB	6371	19336;19337;19338	chr2:178727303;178727302;178727301	chr2:179592030;179592029;179592028
N2A	5444	16555;16556;16557	chr2:178727303;178727302;178727301	chr2:179592030;179592029;179592028
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-51
• Domain position: 22
• Structural Position: 31
• Q(SASA): 0.3565
• 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
E/A	rs1035063547	-0.959	0.993	N	0.639	0.479	0.568285537894	gnomAD-2.1.1	8.07E-06	None	None	None	None	N	None	1.294E-04	0	None	0	0	None	0	None	0	0	0
E/A	rs1035063547	-0.959	0.993	N	0.639	0.479	0.568285537894	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	7.24E-05	0	0	0	0	None	0	0	0	0	0
E/A	rs1035063547	-0.959	0.993	N	0.639	0.479	0.568285537894	gnomAD-4.0.0	6.41213E-06	None	None	None	None	N	None	8.46052E-05	0	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
E/A	0.2985	likely_benign	0.3397	benign	-0.702	Destabilizing	0.993	D	0.639	neutral	N	0.489544351	None	None	N
E/C	0.9566	likely_pathogenic	0.964	pathogenic	-0.54	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
E/D	0.3084	likely_benign	0.2569	benign	-1.099	Destabilizing	0.026	N	0.269	neutral	N	0.498761063	None	None	N
E/F	0.8943	likely_pathogenic	0.9007	pathogenic	-0.069	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
E/G	0.5243	ambiguous	0.5429	ambiguous	-1.061	Destabilizing	0.999	D	0.709	prob.delet.	N	0.512790395	None	None	N
E/H	0.7479	likely_pathogenic	0.7563	pathogenic	-0.273	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
E/I	0.6093	likely_pathogenic	0.6095	pathogenic	0.271	Stabilizing	0.999	D	0.787	deleterious	None	None	None	None	N
E/K	0.5503	ambiguous	0.5953	pathogenic	-0.683	Destabilizing	0.996	D	0.523	neutral	D	0.530115239	None	None	N
E/L	0.7064	likely_pathogenic	0.7241	pathogenic	0.271	Stabilizing	0.999	D	0.759	deleterious	None	None	None	None	N
E/M	0.7359	likely_pathogenic	0.7529	pathogenic	0.545	Stabilizing	0.999	D	0.762	deleterious	None	None	None	None	N
E/N	0.6373	likely_pathogenic	0.6148	pathogenic	-1.161	Destabilizing	0.992	D	0.702	prob.neutral	None	None	None	None	N
E/P	0.9783	likely_pathogenic	0.9745	pathogenic	-0.032	Destabilizing	0.996	D	0.792	deleterious	None	None	None	None	N
E/Q	0.2403	likely_benign	0.2716	benign	-1.015	Destabilizing	0.998	D	0.651	neutral	N	0.486404026	None	None	N
E/R	0.6494	likely_pathogenic	0.6903	pathogenic	-0.322	Destabilizing	0.999	D	0.725	prob.delet.	None	None	None	None	N
E/S	0.3964	ambiguous	0.4061	ambiguous	-1.43	Destabilizing	0.989	D	0.571	neutral	None	None	None	None	N
E/T	0.4362	ambiguous	0.4326	ambiguous	-1.138	Destabilizing	0.999	D	0.746	deleterious	None	None	None	None	N
E/V	0.3786	ambiguous	0.3893	ambiguous	-0.032	Destabilizing	0.999	D	0.751	deleterious	N	0.497572975	None	None	N
E/W	0.9705	likely_pathogenic	0.975	pathogenic	0.164	Stabilizing	1.0	D	0.766	deleterious	None	None	None	None	N
E/Y	0.8537	likely_pathogenic	0.8667	pathogenic	0.161	Stabilizing	1.0	D	0.779	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.