TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8518	25777;25778;25779	chr2:178717182;178717181;178717180	chr2:179581909;179581908;179581907
N2AB	8201	24826;24827;24828	chr2:178717182;178717181;178717180	chr2:179581909;179581908;179581907
N2A	7274	22045;22046;22047	chr2:178717182;178717181;178717180	chr2:179581909;179581908;179581907
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: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-70
• Domain position: 63
• Structural Position: 144
• Q(SASA): 0.0963
• 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
V/L	None	None	0.005	N	0.41	0.156	0.334659703779	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
V/A	0.1936	likely_benign	0.1905	benign	-1.865	Destabilizing	0.001	N	0.163	neutral	N	0.479803849	None	None	N
V/C	0.9122	likely_pathogenic	0.9213	pathogenic	-1.748	Destabilizing	0.002	N	0.419	neutral	None	None	None	None	N
V/D	0.974	likely_pathogenic	0.9731	pathogenic	-1.845	Destabilizing	0.993	D	0.627	neutral	None	None	None	None	N
V/E	0.9476	likely_pathogenic	0.9506	pathogenic	-1.756	Destabilizing	0.942	D	0.595	neutral	D	0.547031257	None	None	N
V/F	0.7572	likely_pathogenic	0.802	pathogenic	-1.302	Destabilizing	0.806	D	0.613	neutral	None	None	None	None	N
V/G	0.5313	ambiguous	0.5374	ambiguous	-2.26	Highly Destabilizing	0.385	N	0.575	neutral	D	0.547031257	None	None	N
V/H	0.9856	likely_pathogenic	0.9874	pathogenic	-1.683	Destabilizing	0.964	D	0.58	neutral	None	None	None	None	N
V/I	0.1234	likely_benign	0.1322	benign	-0.826	Destabilizing	None	N	0.228	neutral	N	0.497319486	None	None	N
V/K	0.9786	likely_pathogenic	0.9797	pathogenic	-1.39	Destabilizing	0.979	D	0.597	neutral	None	None	None	None	N
V/L	0.4798	ambiguous	0.5616	ambiguous	-0.826	Destabilizing	0.005	N	0.41	neutral	N	0.49214538	None	None	N
V/M	0.4381	ambiguous	0.5005	ambiguous	-0.954	Destabilizing	0.748	D	0.537	neutral	None	None	None	None	N
V/N	0.9091	likely_pathogenic	0.9102	pathogenic	-1.41	Destabilizing	0.955	D	0.641	neutral	None	None	None	None	N
V/P	0.8757	likely_pathogenic	0.8696	pathogenic	-1.142	Destabilizing	0.876	D	0.589	neutral	None	None	None	None	N
V/Q	0.9492	likely_pathogenic	0.9565	pathogenic	-1.493	Destabilizing	0.99	D	0.589	neutral	None	None	None	None	N
V/R	0.9604	likely_pathogenic	0.9634	pathogenic	-1.02	Destabilizing	0.99	D	0.645	neutral	None	None	None	None	N
V/S	0.5587	ambiguous	0.5447	ambiguous	-2.086	Highly Destabilizing	0.111	N	0.533	neutral	None	None	None	None	N
V/T	0.2908	likely_benign	0.2665	benign	-1.872	Destabilizing	0.091	N	0.499	neutral	None	None	None	None	N
V/W	0.9903	likely_pathogenic	0.9927	pathogenic	-1.509	Destabilizing	0.99	D	0.601	neutral	None	None	None	None	N
V/Y	0.9682	likely_pathogenic	0.9751	pathogenic	-1.204	Destabilizing	0.766	D	0.626	neutral	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.