TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22656	68191;68192;68193	chr2:178579064;178579063;178579062	chr2:179443791;179443790;179443789
N2AB	21015	63268;63269;63270	chr2:178579064;178579063;178579062	chr2:179443791;179443790;179443789
N2A	20088	60487;60488;60489	chr2:178579064;178579063;178579062	chr2:179443791;179443790;179443789
N2B	13591	40996;40997;40998	chr2:178579064;178579063;178579062	chr2:179443791;179443790;179443789
Novex-1	13716	41371;41372;41373	chr2:178579064;178579063;178579062	chr2:179443791;179443790;179443789
Novex-2	13783	41572;41573;41574	chr2:178579064;178579063;178579062	chr2:179443791;179443790;179443789
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: Fn3-52
• Domain position: 14
• Structural Position: 15
• Q(SASA): 0.1928
• 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/D	rs758038684	-2.029	0.999	N	0.727	0.548	0.811529650169	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
V/D	rs758038684	-2.029	0.999	N	0.727	0.548	0.811529650169	gnomAD-4.0.0	1.09505E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.43942E-05	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	0.4433	ambiguous	0.4101	ambiguous	-1.644	Destabilizing	0.948	D	0.493	neutral	N	0.510614254	None	None	N
V/C	0.84	likely_pathogenic	0.8288	pathogenic	-1.195	Destabilizing	1.0	D	0.609	neutral	None	None	None	None	N
V/D	0.8094	likely_pathogenic	0.7794	pathogenic	-1.697	Destabilizing	0.999	D	0.727	prob.delet.	N	0.520609576	None	None	N
V/E	0.638	likely_pathogenic	0.5898	pathogenic	-1.701	Destabilizing	0.999	D	0.652	neutral	None	None	None	None	N
V/F	0.4171	ambiguous	0.3666	ambiguous	-1.418	Destabilizing	0.997	D	0.64	neutral	N	0.489783117	None	None	N
V/G	0.5411	ambiguous	0.529	ambiguous	-1.971	Destabilizing	0.999	D	0.693	prob.neutral	N	0.491998389	None	None	N
V/H	0.8782	likely_pathogenic	0.859	pathogenic	-1.561	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
V/I	0.0719	likely_benign	0.0678	benign	-0.835	Destabilizing	0.198	N	0.19	neutral	N	0.450813802	None	None	N
V/K	0.6428	likely_pathogenic	0.6021	pathogenic	-1.315	Destabilizing	0.999	D	0.659	neutral	None	None	None	None	N
V/L	0.3569	ambiguous	0.3119	benign	-0.835	Destabilizing	0.9	D	0.313	neutral	N	0.516654792	None	None	N
V/M	0.2286	likely_benign	0.1934	benign	-0.581	Destabilizing	0.998	D	0.566	neutral	None	None	None	None	N
V/N	0.6494	likely_pathogenic	0.6249	pathogenic	-1.115	Destabilizing	0.999	D	0.727	prob.delet.	None	None	None	None	N
V/P	0.8482	likely_pathogenic	0.7756	pathogenic	-1.071	Destabilizing	0.999	D	0.662	neutral	None	None	None	None	N
V/Q	0.6568	likely_pathogenic	0.623	pathogenic	-1.316	Destabilizing	0.999	D	0.661	neutral	None	None	None	None	N
V/R	0.6568	likely_pathogenic	0.6327	pathogenic	-0.789	Destabilizing	0.999	D	0.725	prob.delet.	None	None	None	None	N
V/S	0.6108	likely_pathogenic	0.5909	pathogenic	-1.64	Destabilizing	0.999	D	0.593	neutral	None	None	None	None	N
V/T	0.4342	ambiguous	0.3988	ambiguous	-1.533	Destabilizing	0.992	D	0.505	neutral	None	None	None	None	N
V/W	0.9431	likely_pathogenic	0.9276	pathogenic	-1.614	Destabilizing	1.0	D	0.673	neutral	None	None	None	None	N
V/Y	0.7862	likely_pathogenic	0.7584	pathogenic	-1.322	Destabilizing	0.999	D	0.653	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.