TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34168	102727;102728;102729	chr2:178534113;178534112;178534111	chr2:179398840;179398839;179398838
N2AB	32527	97804;97805;97806	chr2:178534113;178534112;178534111	chr2:179398840;179398839;179398838
N2A	31600	95023;95024;95025	chr2:178534113;178534112;178534111	chr2:179398840;179398839;179398838
N2B	25103	75532;75533;75534	chr2:178534113;178534112;178534111	chr2:179398840;179398839;179398838
Novex-1	25228	75907;75908;75909	chr2:178534113;178534112;178534111	chr2:179398840;179398839;179398838
Novex-2	25295	76108;76109;76110	chr2:178534113;178534112;178534111	chr2:179398840;179398839;179398838
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-160
• Domain position: 32
• Structural Position: 46
• Q(SASA): 0.1641
• 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/A	rs1022062534	None	0.999	D	0.619	0.779	0.802205998338	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
V/A	rs1022062534	None	0.999	D	0.619	0.779	0.802205998338	gnomAD-4.0.0	3.04488E-06	None	None	None	None	N	None	5.24219E-05	0	None	0	0	None	0	0	0	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	0.7389	likely_pathogenic	0.7103	pathogenic	-1.646	Destabilizing	0.999	D	0.619	neutral	D	0.551333465	None	None	N
V/C	0.9711	likely_pathogenic	0.9731	pathogenic	-0.962	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
V/D	0.9906	likely_pathogenic	0.9886	pathogenic	-1.836	Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
V/E	0.9732	likely_pathogenic	0.9686	pathogenic	-1.711	Destabilizing	1.0	D	0.859	deleterious	D	0.577880598	None	None	N
V/F	0.8791	likely_pathogenic	0.853	pathogenic	-1.043	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
V/G	0.8798	likely_pathogenic	0.8535	pathogenic	-2.087	Highly Destabilizing	1.0	D	0.863	deleterious	D	0.577880598	None	None	N
V/H	0.9929	likely_pathogenic	0.9917	pathogenic	-1.784	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
V/I	0.1822	likely_benign	0.1739	benign	-0.47	Destabilizing	0.998	D	0.583	neutral	None	None	None	None	N
V/K	0.9744	likely_pathogenic	0.9688	pathogenic	-1.379	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
V/L	0.8212	likely_pathogenic	0.7972	pathogenic	-0.47	Destabilizing	0.997	D	0.643	neutral	D	0.562336452	None	None	N
V/M	0.7476	likely_pathogenic	0.719	pathogenic	-0.336	Destabilizing	1.0	D	0.723	prob.delet.	D	0.561457628	None	None	N
V/N	0.9743	likely_pathogenic	0.9695	pathogenic	-1.378	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
V/P	0.972	likely_pathogenic	0.9619	pathogenic	-0.831	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
V/Q	0.9742	likely_pathogenic	0.9705	pathogenic	-1.364	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
V/R	0.9691	likely_pathogenic	0.962	pathogenic	-1.089	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
V/S	0.925	likely_pathogenic	0.9156	pathogenic	-1.933	Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
V/T	0.8276	likely_pathogenic	0.8206	pathogenic	-1.68	Destabilizing	0.999	D	0.651	neutral	None	None	None	None	N
V/W	0.9975	likely_pathogenic	0.9969	pathogenic	-1.456	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
V/Y	0.9825	likely_pathogenic	0.9786	pathogenic	-1.07	Destabilizing	1.0	D	0.767	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.