TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26566	79921;79922;79923	chr2:178566436;178566435;178566434	chr2:179431163;179431162;179431161
N2AB	24925	74998;74999;75000	chr2:178566436;178566435;178566434	chr2:179431163;179431162;179431161
N2A	23998	72217;72218;72219	chr2:178566436;178566435;178566434	chr2:179431163;179431162;179431161
N2B	17501	52726;52727;52728	chr2:178566436;178566435;178566434	chr2:179431163;179431162;179431161
Novex-1	17626	53101;53102;53103	chr2:178566436;178566435;178566434	chr2:179431163;179431162;179431161
Novex-2	17693	53302;53303;53304	chr2:178566436;178566435;178566434	chr2:179431163;179431162;179431161
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Fn3-81
• Domain position: 80
• Structural Position: 111
• Q(SASA): 0.1463
• 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
L/I	None	None	0.006	N	0.186	0.074	0.236890367714	gnomAD-4.0.0	1.36872E-06	None	None	None	None	I	None	0	0	None	0	0	None	1.8814E-05	0	8.9952E-07	0	0
L/P	None	None	0.99	N	0.773	0.533	0.843610822603	gnomAD-4.0.0	3.24087E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.4125E-05	0	3.66327E-05

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
L/A	0.2573	likely_benign	0.3019	benign	-2.196	Highly Destabilizing	0.754	D	0.561	neutral	None	None	None	None	I
L/C	0.3555	ambiguous	0.398	ambiguous	-1.607	Destabilizing	0.998	D	0.636	neutral	None	None	None	None	I
L/D	0.8246	likely_pathogenic	0.877	pathogenic	-1.763	Destabilizing	0.993	D	0.77	deleterious	None	None	None	None	I
L/E	0.4107	ambiguous	0.4871	ambiguous	-1.656	Destabilizing	0.978	D	0.749	deleterious	None	None	None	None	I
L/F	0.1092	likely_benign	0.1221	benign	-1.391	Destabilizing	0.942	D	0.504	neutral	N	0.492969856	None	None	I
L/G	0.6347	likely_pathogenic	0.7067	pathogenic	-2.622	Highly Destabilizing	0.978	D	0.741	deleterious	None	None	None	None	I
L/H	0.2363	likely_benign	0.2782	benign	-1.817	Destabilizing	0.997	D	0.771	deleterious	N	0.482272859	None	None	I
L/I	0.0693	likely_benign	0.0701	benign	-1.028	Destabilizing	0.006	N	0.186	neutral	N	0.405369514	None	None	I
L/K	0.2723	likely_benign	0.3246	benign	-1.456	Destabilizing	0.978	D	0.702	prob.neutral	None	None	None	None	I
L/M	0.0778	likely_benign	0.0831	benign	-0.992	Destabilizing	0.956	D	0.535	neutral	None	None	None	None	I
L/N	0.4946	ambiguous	0.5667	pathogenic	-1.458	Destabilizing	0.993	D	0.773	deleterious	None	None	None	None	I
L/P	0.9597	likely_pathogenic	0.9662	pathogenic	-1.392	Destabilizing	0.99	D	0.773	deleterious	N	0.489552399	None	None	I
L/Q	0.1457	likely_benign	0.1733	benign	-1.523	Destabilizing	0.993	D	0.731	prob.delet.	None	None	None	None	I
L/R	0.2148	likely_benign	0.2575	benign	-1.009	Destabilizing	0.97	D	0.727	prob.delet.	N	0.476498893	None	None	I
L/S	0.311	likely_benign	0.3547	ambiguous	-2.222	Highly Destabilizing	0.978	D	0.655	neutral	None	None	None	None	I
L/T	0.1999	likely_benign	0.23	benign	-1.987	Destabilizing	0.86	D	0.573	neutral	None	None	None	None	I
L/V	0.0668	likely_benign	0.0702	benign	-1.392	Destabilizing	0.014	N	0.247	neutral	N	0.362938527	None	None	I
L/W	0.2313	likely_benign	0.2737	benign	-1.537	Destabilizing	0.998	D	0.713	prob.delet.	None	None	None	None	I
L/Y	0.2821	likely_benign	0.3255	benign	-1.3	Destabilizing	0.978	D	0.66	neutral	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.