TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8002	24229;24230;24231	chr2:178719386;178719385;178719384	chr2:179584113;179584112;179584111
N2AB	7685	23278;23279;23280	chr2:178719386;178719385;178719384	chr2:179584113;179584112;179584111
N2A	6758	20497;20498;20499	chr2:178719386;178719385;178719384	chr2:179584113;179584112;179584111
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: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-65
• Domain position: 18
• Structural Position: 28
• Q(SASA): 0.2476
• 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/A	None	None	None	N	0.132	0.074	0.149567049428	gnomAD-4.0.0	2.05267E-06	None	None	None	None	I	None	0	0	None	0	2.51915E-05	None	0	0	1.799E-06	0	0
V/F	rs1332361126	-1.004	0.317	N	0.723	0.184	0.3691244813	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
V/F	rs1332361126	-1.004	0.317	N	0.723	0.184	0.3691244813	gnomAD-4.0.0	3.18264E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.7171E-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	0.0782	likely_benign	0.08	benign	-1.508	Destabilizing	None	N	0.132	neutral	N	0.446186268	None	None	I
V/C	0.5465	ambiguous	0.56	ambiguous	-1.379	Destabilizing	0.824	D	0.689	prob.neutral	None	None	None	None	I
V/D	0.4151	ambiguous	0.4623	ambiguous	-0.843	Destabilizing	0.317	N	0.731	prob.delet.	D	0.522053336	None	None	I
V/E	0.3696	ambiguous	0.411	ambiguous	-0.771	Destabilizing	0.149	N	0.68	prob.neutral	None	None	None	None	I
V/F	0.1668	likely_benign	0.1954	benign	-0.977	Destabilizing	0.317	N	0.723	prob.delet.	N	0.509373742	None	None	I
V/G	0.177	likely_benign	0.1848	benign	-1.894	Destabilizing	None	N	0.417	neutral	N	0.469208602	None	None	I
V/H	0.5178	ambiguous	0.5606	ambiguous	-1.251	Destabilizing	0.935	D	0.727	prob.delet.	None	None	None	None	I
V/I	0.0727	likely_benign	0.0819	benign	-0.526	Destabilizing	None	N	0.271	neutral	N	0.478010685	None	None	I
V/K	0.4022	ambiguous	0.4222	ambiguous	-1.256	Destabilizing	0.149	N	0.684	prob.neutral	None	None	None	None	I
V/L	0.1393	likely_benign	0.1715	benign	-0.526	Destabilizing	0.009	N	0.461	neutral	N	0.469889847	None	None	I
V/M	0.1078	likely_benign	0.1214	benign	-0.635	Destabilizing	0.38	N	0.611	neutral	None	None	None	None	I
V/N	0.2676	likely_benign	0.3149	benign	-1.233	Destabilizing	0.38	N	0.737	prob.delet.	None	None	None	None	I
V/P	0.6128	likely_pathogenic	0.6873	pathogenic	-0.819	Destabilizing	0.38	N	0.721	prob.delet.	None	None	None	None	I
V/Q	0.3681	ambiguous	0.3908	ambiguous	-1.232	Destabilizing	0.555	D	0.723	prob.delet.	None	None	None	None	I
V/R	0.324	likely_benign	0.3456	ambiguous	-0.891	Destabilizing	0.38	N	0.74	deleterious	None	None	None	None	I
V/S	0.148	likely_benign	0.1622	benign	-1.911	Destabilizing	0.081	N	0.589	neutral	None	None	None	None	I
V/T	0.1028	likely_benign	0.1106	benign	-1.689	Destabilizing	0.002	N	0.26	neutral	None	None	None	None	I
V/W	0.7404	likely_pathogenic	0.7938	pathogenic	-1.141	Destabilizing	0.935	D	0.727	prob.delet.	None	None	None	None	I
V/Y	0.4819	ambiguous	0.5322	ambiguous	-0.848	Destabilizing	0.555	D	0.727	prob.delet.	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.