TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26719	80380;80381;80382	chr2:178565977;178565976;178565975	chr2:179430704;179430703;179430702
N2AB	25078	75457;75458;75459	chr2:178565977;178565976;178565975	chr2:179430704;179430703;179430702
N2A	24151	72676;72677;72678	chr2:178565977;178565976;178565975	chr2:179430704;179430703;179430702
N2B	17654	53185;53186;53187	chr2:178565977;178565976;178565975	chr2:179430704;179430703;179430702
Novex-1	17779	53560;53561;53562	chr2:178565977;178565976;178565975	chr2:179430704;179430703;179430702
Novex-2	17846	53761;53762;53763	chr2:178565977;178565976;178565975	chr2:179430704;179430703;179430702
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: Fn3-82
• Domain position: 37
• Structural Position: 39
• Q(SASA): 0.1755
• 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	0.517	N	0.541	0.335	0.501060295512	gnomAD-4.0.0	5.47426E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.29688E-06	0	1.65684E-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	0.4703	ambiguous	0.5363	ambiguous	-2.068	Highly Destabilizing	0.517	D	0.541	neutral	N	0.476520118	None	None	N
V/C	0.6669	likely_pathogenic	0.7327	pathogenic	-1.974	Destabilizing	0.996	D	0.655	neutral	None	None	None	None	N
V/D	0.8145	likely_pathogenic	0.8752	pathogenic	-3.052	Highly Destabilizing	0.987	D	0.718	prob.delet.	None	None	None	None	N
V/E	0.6379	likely_pathogenic	0.7622	pathogenic	-2.957	Highly Destabilizing	0.983	D	0.663	neutral	N	0.511280684	None	None	N
V/F	0.2347	likely_benign	0.2783	benign	-1.492	Destabilizing	0.923	D	0.638	neutral	None	None	None	None	N
V/G	0.6008	likely_pathogenic	0.6595	pathogenic	-2.471	Highly Destabilizing	0.949	D	0.687	prob.neutral	N	0.486181357	None	None	N
V/H	0.6387	likely_pathogenic	0.7291	pathogenic	-1.973	Destabilizing	0.996	D	0.718	prob.delet.	None	None	None	None	N
V/I	0.0667	likely_benign	0.07	benign	-0.99	Destabilizing	0.005	N	0.247	neutral	None	None	None	None	N
V/K	0.5992	likely_pathogenic	0.7275	pathogenic	-1.801	Destabilizing	0.961	D	0.652	neutral	None	None	None	None	N
V/L	0.2001	likely_benign	0.2321	benign	-0.99	Destabilizing	0.003	N	0.287	neutral	N	0.463780312	None	None	N
V/M	0.1689	likely_benign	0.2155	benign	-1.003	Destabilizing	0.901	D	0.629	neutral	N	0.474913957	None	None	N
V/N	0.531	ambiguous	0.6157	pathogenic	-1.992	Destabilizing	0.987	D	0.72	prob.delet.	None	None	None	None	N
V/P	0.9923	likely_pathogenic	0.9922	pathogenic	-1.321	Destabilizing	0.987	D	0.669	neutral	None	None	None	None	N
V/Q	0.4968	ambiguous	0.6261	pathogenic	-2.081	Highly Destabilizing	0.987	D	0.675	prob.neutral	None	None	None	None	N
V/R	0.4874	ambiguous	0.616	pathogenic	-1.307	Destabilizing	0.987	D	0.718	prob.delet.	None	None	None	None	N
V/S	0.4832	ambiguous	0.5532	ambiguous	-2.498	Highly Destabilizing	0.961	D	0.644	neutral	None	None	None	None	N
V/T	0.3657	ambiguous	0.4224	ambiguous	-2.289	Highly Destabilizing	0.775	D	0.583	neutral	None	None	None	None	N
V/W	0.8419	likely_pathogenic	0.884	pathogenic	-1.861	Destabilizing	0.996	D	0.719	prob.delet.	None	None	None	None	N
V/Y	0.6132	likely_pathogenic	0.6778	pathogenic	-1.558	Destabilizing	0.961	D	0.659	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.