TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5666	17221;17222;17223	chr2:178731879;178731878;178731877	chr2:179596606;179596605;179596604
N2AB	5349	16270;16271;16272	chr2:178731879;178731878;178731877	chr2:179596606;179596605;179596604
N2A	4422	13489;13490;13491	chr2:178731879;178731878;178731877	chr2:179596606;179596605;179596604
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: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Ig-40
• Domain position: 30
• Structural Position: 44
• Q(SASA): 0.2035
• 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
F/L	None	None	0.008	N	0.21	0.339	0.190952846119	gnomAD-4.0.0	3.18275E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85851E-06	1.43279E-05	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
F/A	0.8327	likely_pathogenic	0.9104	pathogenic	-2.955	Highly Destabilizing	0.775	D	0.563	neutral	None	None	None	None	I
F/C	0.6271	likely_pathogenic	0.7973	pathogenic	-1.78	Destabilizing	0.995	D	0.64	neutral	N	0.504392923	None	None	I
F/D	0.9772	likely_pathogenic	0.9894	pathogenic	-2.383	Highly Destabilizing	0.987	D	0.701	prob.neutral	None	None	None	None	I
F/E	0.9762	likely_pathogenic	0.9885	pathogenic	-2.244	Highly Destabilizing	0.961	D	0.701	prob.neutral	None	None	None	None	I
F/G	0.9493	likely_pathogenic	0.9751	pathogenic	-3.356	Highly Destabilizing	0.961	D	0.665	neutral	None	None	None	None	I
F/H	0.8755	likely_pathogenic	0.9261	pathogenic	-1.603	Destabilizing	0.923	D	0.574	neutral	None	None	None	None	I
F/I	0.5046	ambiguous	0.6623	pathogenic	-1.681	Destabilizing	0.565	D	0.499	neutral	N	0.499925618	None	None	I
F/K	0.9756	likely_pathogenic	0.9887	pathogenic	-2.072	Highly Destabilizing	0.961	D	0.698	prob.neutral	None	None	None	None	I
F/L	0.8893	likely_pathogenic	0.9389	pathogenic	-1.681	Destabilizing	0.008	N	0.21	neutral	N	0.482222505	None	None	I
F/M	0.691	likely_pathogenic	0.8071	pathogenic	-1.258	Destabilizing	0.923	D	0.477	neutral	None	None	None	None	I
F/N	0.928	likely_pathogenic	0.9627	pathogenic	-2.233	Highly Destabilizing	0.961	D	0.708	prob.delet.	None	None	None	None	I
F/P	0.9769	likely_pathogenic	0.9883	pathogenic	-2.11	Highly Destabilizing	0.987	D	0.706	prob.neutral	None	None	None	None	I
F/Q	0.9519	likely_pathogenic	0.9748	pathogenic	-2.298	Highly Destabilizing	0.961	D	0.707	prob.neutral	None	None	None	None	I
F/R	0.9428	likely_pathogenic	0.9705	pathogenic	-1.343	Destabilizing	0.961	D	0.707	prob.neutral	None	None	None	None	I
F/S	0.7857	likely_pathogenic	0.8938	pathogenic	-3.008	Highly Destabilizing	0.901	D	0.602	neutral	N	0.512470841	None	None	I
F/T	0.8556	likely_pathogenic	0.93	pathogenic	-2.767	Highly Destabilizing	0.961	D	0.601	neutral	None	None	None	None	I
F/V	0.463	ambiguous	0.625	pathogenic	-2.11	Highly Destabilizing	0.565	D	0.494	neutral	N	0.482147934	None	None	I
F/W	0.6634	likely_pathogenic	0.7407	pathogenic	-0.694	Destabilizing	0.989	D	0.477	neutral	None	None	None	None	I
F/Y	0.3056	likely_benign	0.3573	ambiguous	-1.05	Destabilizing	0.008	N	0.279	neutral	N	0.492783128	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.