TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5912	17959;17960;17961	chr2:178730931;178730930;178730929	chr2:179595658;179595657;179595656
N2AB	5595	17008;17009;17010	chr2:178730931;178730930;178730929	chr2:179595658;179595657;179595656
N2A	4668	14227;14228;14229	chr2:178730931;178730930;178730929	chr2:179595658;179595657;179595656
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-42
• Domain position: 90
• Structural Position: 176
• Q(SASA): 1.0185
• 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/I	rs879030996	None	0.767	D	0.565	0.312	None	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
V/I	rs879030996	None	0.767	D	0.565	0.312	None	gnomAD-4.0.0	2.49949E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.55864E-06	0	1.6153E-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
V/A	0.907	likely_pathogenic	0.9239	pathogenic	-1.526	Destabilizing	0.998	D	0.761	deleterious	D	0.608535255	None	None	N
V/C	0.9823	likely_pathogenic	0.9852	pathogenic	-1.675	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
V/D	0.9928	likely_pathogenic	0.9962	pathogenic	-2.793	Highly Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
V/E	0.9843	likely_pathogenic	0.9907	pathogenic	-2.773	Highly Destabilizing	1.0	D	0.781	deleterious	D	0.609140668	None	None	N
V/F	0.9373	likely_pathogenic	0.9536	pathogenic	-1.316	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
V/G	0.9303	likely_pathogenic	0.9526	pathogenic	-1.819	Destabilizing	1.0	D	0.761	deleterious	D	0.609140668	None	None	N
V/H	0.9963	likely_pathogenic	0.9978	pathogenic	-1.294	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
V/I	0.1333	likely_benign	0.1363	benign	-0.794	Destabilizing	0.767	D	0.565	neutral	D	0.525027212	None	None	N
V/K	0.9918	likely_pathogenic	0.9949	pathogenic	-1.345	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
V/L	0.8824	likely_pathogenic	0.889	pathogenic	-0.794	Destabilizing	0.981	D	0.766	deleterious	D	0.558226965	None	None	N
V/M	0.8652	likely_pathogenic	0.8792	pathogenic	-0.849	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
V/N	0.9762	likely_pathogenic	0.9863	pathogenic	-1.477	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
V/P	0.9826	likely_pathogenic	0.9878	pathogenic	-1.009	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
V/Q	0.9888	likely_pathogenic	0.993	pathogenic	-1.713	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	N
V/R	0.9848	likely_pathogenic	0.9907	pathogenic	-0.835	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
V/S	0.9472	likely_pathogenic	0.9631	pathogenic	-1.839	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
V/T	0.8783	likely_pathogenic	0.8956	pathogenic	-1.722	Destabilizing	0.998	D	0.786	deleterious	None	None	None	None	N
V/W	0.9991	likely_pathogenic	0.9994	pathogenic	-1.563	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
V/Y	0.993	likely_pathogenic	0.9954	pathogenic	-1.22	Destabilizing	1.0	D	0.813	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.