TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14515	43768;43769;43770	chr2:178632351;178632350;178632349	chr2:179497078;179497077;179497076
N2AB	12874	38845;38846;38847	chr2:178632351;178632350;178632349	chr2:179497078;179497077;179497076
N2A	11947	36064;36065;36066	chr2:178632351;178632350;178632349	chr2:179497078;179497077;179497076
N2B	5450	16573;16574;16575	chr2:178632351;178632350;178632349	chr2:179497078;179497077;179497076
Novex-1	5575	16948;16949;16950	chr2:178632351;178632350;178632349	chr2:179497078;179497077;179497076
Novex-2	5642	17149;17150;17151	chr2:178632351;178632350;178632349	chr2:179497078;179497077;179497076
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-96
• Domain position: 19
• Structural Position: 29
• Q(SASA): 0.2625
• 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	None	None	0.625	D	0.556	0.396	0.716962004524	gnomAD-4.0.0	1.61086E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.46289E-05	0
V/L	None	None	0.625	D	0.602	0.401	0.611273083002	gnomAD-4.0.0	8.40227E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.18753E-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	0.2028	likely_benign	0.1747	benign	-0.924	Destabilizing	0.625	D	0.556	neutral	D	0.589378312	None	None	N
V/C	0.7999	likely_pathogenic	0.7672	pathogenic	-0.87	Destabilizing	0.998	D	0.563	neutral	None	None	None	None	N
V/D	0.3048	likely_benign	0.2648	benign	-0.003	Destabilizing	0.728	D	0.523	neutral	None	None	None	None	N
V/E	0.2025	likely_benign	0.1689	benign	-0.01	Destabilizing	0.002	N	0.469	neutral	N	0.472078588	None	None	N
V/F	0.2037	likely_benign	0.1796	benign	-0.648	Destabilizing	0.991	D	0.569	neutral	None	None	None	None	N
V/G	0.2585	likely_benign	0.2319	benign	-1.202	Destabilizing	0.801	D	0.547	neutral	D	0.588302929	None	None	N
V/H	0.5498	ambiguous	0.485	ambiguous	-0.556	Destabilizing	0.993	D	0.635	neutral	None	None	None	None	N
V/I	0.0856	likely_benign	0.0796	benign	-0.287	Destabilizing	0.771	D	0.567	neutral	D	0.543558498	None	None	N
V/K	0.2585	likely_benign	0.2225	benign	-0.602	Destabilizing	0.728	D	0.521	neutral	None	None	None	None	N
V/L	0.2042	likely_benign	0.1825	benign	-0.287	Destabilizing	0.625	D	0.602	neutral	D	0.590157361	None	None	N
V/M	0.146	likely_benign	0.1357	benign	-0.437	Destabilizing	0.991	D	0.587	neutral	None	None	None	None	N
V/N	0.2485	likely_benign	0.2145	benign	-0.477	Destabilizing	0.949	D	0.615	neutral	None	None	None	None	N
V/P	0.8285	likely_pathogenic	0.8078	pathogenic	-0.463	Destabilizing	0.974	D	0.589	neutral	None	None	None	None	N
V/Q	0.275	likely_benign	0.2431	benign	-0.563	Destabilizing	0.728	D	0.569	neutral	None	None	None	None	N
V/R	0.2518	likely_benign	0.2336	benign	-0.21	Destabilizing	0.949	D	0.615	neutral	None	None	None	None	N
V/S	0.197	likely_benign	0.1793	benign	-1.088	Destabilizing	0.842	D	0.511	neutral	None	None	None	None	N
V/T	0.1609	likely_benign	0.1434	benign	-0.962	Destabilizing	0.842	D	0.555	neutral	None	None	None	None	N
V/W	0.8507	likely_pathogenic	0.8118	pathogenic	-0.757	Destabilizing	0.998	D	0.673	neutral	None	None	None	None	N
V/Y	0.5921	likely_pathogenic	0.5343	ambiguous	-0.452	Destabilizing	0.991	D	0.568	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.