TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31305	94138;94139;94140	chr2:178547713;178547712;178547711	chr2:179412440;179412439;179412438
N2AB	29664	89215;89216;89217	chr2:178547713;178547712;178547711	chr2:179412440;179412439;179412438
N2A	28737	86434;86435;86436	chr2:178547713;178547712;178547711	chr2:179412440;179412439;179412438
N2B	22240	66943;66944;66945	chr2:178547713;178547712;178547711	chr2:179412440;179412439;179412438
Novex-1	22365	67318;67319;67320	chr2:178547713;178547712;178547711	chr2:179412440;179412439;179412438
Novex-2	22432	67519;67520;67521	chr2:178547713;178547712;178547711	chr2:179412440;179412439;179412438
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-151
• Domain position: 88
• Structural Position: 177
• Q(SASA): 0.8109
• 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
V/I	rs763095452	-0.064	0.767	D	0.575	0.308	0.68354922304	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	4.64E-05	0	0
V/I	rs763095452	-0.064	0.767	D	0.575	0.308	0.68354922304	gnomAD-4.0.0	1.59105E-06	None	None	None	None	I	None	0	0	None	0	0	None	1.88239E-05	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	0.9189	likely_pathogenic	0.8467	pathogenic	-1.812	Destabilizing	0.998	D	0.707	prob.neutral	D	0.609231749	None	None	I
V/C	0.976	likely_pathogenic	0.9585	pathogenic	-1.891	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	I
V/D	0.9965	likely_pathogenic	0.9949	pathogenic	-2.588	Highly Destabilizing	1.0	D	0.755	deleterious	D	0.609837162	None	None	I
V/E	0.9914	likely_pathogenic	0.9878	pathogenic	-2.528	Highly Destabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	I
V/F	0.9454	likely_pathogenic	0.935	pathogenic	-1.382	Destabilizing	0.999	D	0.767	deleterious	D	0.609231749	None	None	I
V/G	0.9541	likely_pathogenic	0.9231	pathogenic	-2.145	Highly Destabilizing	1.0	D	0.715	prob.delet.	D	0.609837162	None	None	I
V/H	0.9976	likely_pathogenic	0.9967	pathogenic	-1.548	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	I
V/I	0.1332	likely_benign	0.1269	benign	-0.954	Destabilizing	0.767	D	0.575	neutral	D	0.545498485	None	None	I
V/K	0.9953	likely_pathogenic	0.9937	pathogenic	-1.48	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	I
V/L	0.9038	likely_pathogenic	0.8485	pathogenic	-0.954	Destabilizing	0.981	D	0.72	prob.delet.	D	0.607213706	None	None	I
V/M	0.8677	likely_pathogenic	0.8061	pathogenic	-1.125	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	I
V/N	0.9775	likely_pathogenic	0.967	pathogenic	-1.595	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	I
V/P	0.9826	likely_pathogenic	0.9711	pathogenic	-1.212	Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	I
V/Q	0.9927	likely_pathogenic	0.9888	pathogenic	-1.764	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	I
V/R	0.992	likely_pathogenic	0.9893	pathogenic	-1.012	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	I
V/S	0.9469	likely_pathogenic	0.9027	pathogenic	-2.092	Highly Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	I
V/T	0.8485	likely_pathogenic	0.7679	pathogenic	-1.925	Destabilizing	0.998	D	0.742	deleterious	None	None	None	None	I
V/W	0.9992	likely_pathogenic	0.999	pathogenic	-1.6	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	I
V/Y	0.9954	likely_pathogenic	0.9938	pathogenic	-1.285	Destabilizing	1.0	D	0.778	deleterious	None	None	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.