TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8721	26386;26387;26388	chr2:178715025;178715024;178715023	chr2:179579752;179579751;179579750
N2AB	8404	25435;25436;25437	chr2:178715025;178715024;178715023	chr2:179579752;179579751;179579750
N2A	7477	22654;22655;22656	chr2:178715025;178715024;178715023	chr2:179579752;179579751;179579750
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-72
• Domain position: 79
• Structural Position: 163
• Q(SASA): 0.8534
• 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/M	rs777730788	-0.331	0.999	N	0.67	0.432	0.641123051583	gnomAD-2.1.1	2.29894E-04	None	None	None	None	I	None	0	0	None	0	0	None	1.84053E-03	None	0	8.92E-06	0
V/M	rs777730788	-0.331	0.999	N	0.67	0.432	0.641123051583	gnomAD-3.1.2	5.26E-05	None	None	None	None	I	None	0	0	0	0	0	None	0	0	0	1.65632E-03	0
V/M	rs777730788	-0.331	0.999	N	0.67	0.432	0.641123051583	gnomAD-4.0.0	1.08498E-04	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.69597E-06	1.84774E-03	8.00846E-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	0.1883	likely_benign	0.263	benign	-0.387	Destabilizing	0.241	N	0.415	neutral	N	0.515529789	None	None	I
V/C	0.872	likely_pathogenic	0.9093	pathogenic	-0.849	Destabilizing	1.0	D	0.655	neutral	None	None	None	None	I
V/D	0.912	likely_pathogenic	0.9633	pathogenic	-0.459	Destabilizing	0.998	D	0.693	prob.neutral	None	None	None	None	I
V/E	0.7945	likely_pathogenic	0.8838	pathogenic	-0.58	Destabilizing	0.985	D	0.665	neutral	N	0.501750031	None	None	I
V/F	0.3388	likely_benign	0.4674	ambiguous	-0.805	Destabilizing	0.999	D	0.655	neutral	None	None	None	None	I
V/G	0.4297	ambiguous	0.5716	pathogenic	-0.426	Destabilizing	0.996	D	0.621	neutral	N	0.511269457	None	None	I
V/H	0.9124	likely_pathogenic	0.954	pathogenic	-0.036	Destabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	I
V/I	0.1233	likely_benign	0.1453	benign	-0.423	Destabilizing	0.803	D	0.526	neutral	None	None	None	None	I
V/K	0.8856	likely_pathogenic	0.9323	pathogenic	-0.429	Destabilizing	0.995	D	0.667	neutral	None	None	None	None	I
V/L	0.5559	ambiguous	0.6617	pathogenic	-0.423	Destabilizing	0.602	D	0.567	neutral	N	0.509662609	None	None	I
V/M	0.3244	likely_benign	0.4358	ambiguous	-0.624	Destabilizing	0.999	D	0.67	neutral	N	0.499939605	None	None	I
V/N	0.7902	likely_pathogenic	0.8913	pathogenic	-0.235	Destabilizing	0.989	D	0.702	prob.neutral	None	None	None	None	I
V/P	0.9785	likely_pathogenic	0.9882	pathogenic	-0.385	Destabilizing	0.966	D	0.677	prob.neutral	None	None	None	None	I
V/Q	0.8156	likely_pathogenic	0.8903	pathogenic	-0.459	Destabilizing	0.998	D	0.687	prob.neutral	None	None	None	None	I
V/R	0.7921	likely_pathogenic	0.8568	pathogenic	0.03	Stabilizing	0.998	D	0.703	prob.neutral	None	None	None	None	I
V/S	0.4238	ambiguous	0.5824	pathogenic	-0.529	Destabilizing	0.982	D	0.592	neutral	None	None	None	None	I
V/T	0.3004	likely_benign	0.4005	ambiguous	-0.565	Destabilizing	0.927	D	0.615	neutral	None	None	None	None	I
V/W	0.9508	likely_pathogenic	0.9758	pathogenic	-0.843	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	I
V/Y	0.8456	likely_pathogenic	0.9095	pathogenic	-0.585	Destabilizing	0.999	D	0.663	neutral	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.