TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25499	76720;76721;76722	chr2:178569637;178569636;178569635	chr2:179434364;179434363;179434362
N2AB	23858	71797;71798;71799	chr2:178569637;178569636;178569635	chr2:179434364;179434363;179434362
N2A	22931	69016;69017;69018	chr2:178569637;178569636;178569635	chr2:179434364;179434363;179434362
N2B	16434	49525;49526;49527	chr2:178569637;178569636;178569635	chr2:179434364;179434363;179434362
Novex-1	16559	49900;49901;49902	chr2:178569637;178569636;178569635	chr2:179434364;179434363;179434362
Novex-2	16626	50101;50102;50103	chr2:178569637;178569636;178569635	chr2:179434364;179434363;179434362
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-73
• Domain position: 95
• Structural Position: 127
• Q(SASA): 0.1673
• 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
I/L	None	None	0.012	N	0.393	0.041	0.0482279557977	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
I/A	0.2686	likely_benign	0.2325	benign	-2.351	Highly Destabilizing	0.034	N	0.631	neutral	None	None	None	None	N
I/C	0.4796	ambiguous	0.4458	ambiguous	-1.573	Destabilizing	0.823	D	0.731	deleterious	None	None	None	None	N
I/D	0.7802	likely_pathogenic	0.7364	pathogenic	-2.622	Highly Destabilizing	0.552	D	0.822	deleterious	None	None	None	None	N
I/E	0.6297	likely_pathogenic	0.594	pathogenic	-2.382	Highly Destabilizing	0.552	D	0.775	deleterious	None	None	None	None	N
I/F	0.1722	likely_benign	0.1606	benign	-1.41	Destabilizing	0.314	N	0.709	prob.delet.	N	0.510080244	None	None	N
I/G	0.6162	likely_pathogenic	0.5359	ambiguous	-2.883	Highly Destabilizing	0.552	D	0.741	deleterious	None	None	None	None	N
I/H	0.4921	ambiguous	0.4607	ambiguous	-2.171	Highly Destabilizing	0.934	D	0.814	deleterious	None	None	None	None	N
I/K	0.4223	ambiguous	0.4021	ambiguous	-1.884	Destabilizing	0.552	D	0.776	deleterious	None	None	None	None	N
I/L	0.1233	likely_benign	0.1149	benign	-0.814	Destabilizing	0.012	N	0.393	neutral	N	0.462112939	None	None	N
I/M	0.1108	likely_benign	0.1003	benign	-0.711	Destabilizing	0.314	N	0.742	deleterious	N	0.4918412	None	None	N
I/N	0.3357	likely_benign	0.3031	benign	-2.314	Highly Destabilizing	0.739	D	0.825	deleterious	N	0.460389375	None	None	N
I/P	0.854	likely_pathogenic	0.8252	pathogenic	-1.308	Destabilizing	0.552	D	0.829	deleterious	None	None	None	None	N
I/Q	0.4292	ambiguous	0.4015	ambiguous	-2.152	Highly Destabilizing	0.789	D	0.821	deleterious	None	None	None	None	N
I/R	0.3507	ambiguous	0.328	benign	-1.636	Destabilizing	0.552	D	0.821	deleterious	None	None	None	None	N
I/S	0.3345	likely_benign	0.2887	benign	-2.982	Highly Destabilizing	0.314	N	0.719	prob.delet.	N	0.457094012	None	None	N
I/T	0.186	likely_benign	0.17	benign	-2.585	Highly Destabilizing	0.061	N	0.702	prob.delet.	N	0.484779155	None	None	N
I/V	0.0502	likely_benign	0.0498	benign	-1.308	Destabilizing	None	N	0.168	neutral	N	0.370240141	None	None	N
I/W	0.8089	likely_pathogenic	0.7821	pathogenic	-1.731	Destabilizing	0.934	D	0.814	deleterious	None	None	None	None	N
I/Y	0.4937	ambiguous	0.4685	ambiguous	-1.42	Destabilizing	0.552	D	0.783	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.