TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9015	27268;27269;27270	chr2:178713091;178713090;178713089	chr2:179577818;179577817;179577816
N2AB	8698	26317;26318;26319	chr2:178713091;178713090;178713089	chr2:179577818;179577817;179577816
N2A	7771	23536;23537;23538	chr2:178713091;178713090;178713089	chr2:179577818;179577817;179577816
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-75
• Domain position: 90
• Structural Position: 177
• Q(SASA): 0.5694
• 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/M	rs1478991979	-0.322	0.638	D	0.724	0.58	0.587237122171	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/M	rs1478991979	-0.322	0.638	D	0.724	0.58	0.587237122171	gnomAD-4.0.0	1.59532E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86804E-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	0.6116	likely_pathogenic	0.6431	pathogenic	-1.383	Destabilizing	0.334	N	0.613	neutral	D	0.629430074	None	None	N
V/C	0.9268	likely_pathogenic	0.9411	pathogenic	-1.492	Destabilizing	0.982	D	0.712	prob.delet.	None	None	None	None	N
V/D	0.9745	likely_pathogenic	0.9794	pathogenic	-2.042	Highly Destabilizing	0.826	D	0.737	prob.delet.	None	None	None	None	N
V/E	0.9179	likely_pathogenic	0.9291	pathogenic	-2.051	Highly Destabilizing	0.781	D	0.711	prob.delet.	D	0.646054848	None	None	N
V/F	0.5516	ambiguous	0.5632	ambiguous	-1.354	Destabilizing	0.7	D	0.699	prob.neutral	None	None	None	None	N
V/G	0.789	likely_pathogenic	0.8059	pathogenic	-1.646	Destabilizing	0.781	D	0.71	prob.delet.	D	0.646054848	None	None	N
V/H	0.9685	likely_pathogenic	0.9757	pathogenic	-1.166	Destabilizing	0.982	D	0.737	prob.delet.	None	None	None	None	N
V/I	0.08	likely_benign	0.0982	benign	-0.756	Destabilizing	0.002	N	0.481	neutral	None	None	None	None	N
V/K	0.9248	likely_pathogenic	0.9426	pathogenic	-1.087	Destabilizing	0.826	D	0.711	prob.delet.	None	None	None	None	N
V/L	0.4375	ambiguous	0.4874	ambiguous	-0.756	Destabilizing	0.034	N	0.63	neutral	D	0.583997241	None	None	N
V/M	0.3749	ambiguous	0.438	ambiguous	-0.765	Destabilizing	0.638	D	0.724	prob.delet.	D	0.620113127	None	None	N
V/N	0.9021	likely_pathogenic	0.9189	pathogenic	-1.082	Destabilizing	0.935	D	0.745	deleterious	None	None	None	None	N
V/P	0.931	likely_pathogenic	0.9358	pathogenic	-0.934	Destabilizing	0.935	D	0.722	prob.delet.	None	None	None	None	N
V/Q	0.9045	likely_pathogenic	0.9173	pathogenic	-1.348	Destabilizing	0.935	D	0.733	prob.delet.	None	None	None	None	N
V/R	0.8883	likely_pathogenic	0.907	pathogenic	-0.608	Destabilizing	0.826	D	0.743	deleterious	None	None	None	None	N
V/S	0.7788	likely_pathogenic	0.7954	pathogenic	-1.521	Destabilizing	0.826	D	0.683	prob.neutral	None	None	None	None	N
V/T	0.651	likely_pathogenic	0.6887	pathogenic	-1.43	Destabilizing	0.399	N	0.67	neutral	None	None	None	None	N
V/W	0.9752	likely_pathogenic	0.9817	pathogenic	-1.513	Destabilizing	0.982	D	0.712	prob.delet.	None	None	None	None	N
V/Y	0.9269	likely_pathogenic	0.9343	pathogenic	-1.157	Destabilizing	0.826	D	0.707	prob.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.