TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6578	19957;19958;19959	chr2:178727846;178727845;178727844	chr2:179592573;179592572;179592571
N2AB	6261	19006;19007;19008	chr2:178727846;178727845;178727844	chr2:179592573;179592572;179592571
N2A	5334	16225;16226;16227	chr2:178727846;178727845;178727844	chr2:179592573;179592572;179592571
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-50
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.5655
• 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/L	rs2079625925	None	0.002	N	0.072	0.197	0.284150004643	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	9.43E-05	0	0	0	0
V/L	rs2079625925	None	0.002	N	0.072	0.197	0.284150004643	gnomAD-4.0.0	6.57618E-06	None	None	None	None	N	None	0	0	None	0	0	None	9.42685E-05	0	0	0	0
V/M	None	None	0.139	N	0.127	0.207	0.342631996419	gnomAD-4.0.0	1.6504E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.9427E-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	0.1387	likely_benign	0.1412	benign	-1.139	Destabilizing	0.139	N	0.153	neutral	N	0.491114134	None	None	N
V/C	0.7179	likely_pathogenic	0.7245	pathogenic	-0.778	Destabilizing	0.995	D	0.317	neutral	None	None	None	None	N
V/D	0.1656	likely_benign	0.1598	benign	-0.789	Destabilizing	0.543	D	0.386	neutral	None	None	None	None	N
V/E	0.0998	likely_benign	0.0945	benign	-0.774	Destabilizing	0.002	N	0.135	neutral	N	0.417771169	None	None	N
V/F	0.1585	likely_benign	0.1568	benign	-0.776	Destabilizing	0.893	D	0.39	neutral	None	None	None	None	N
V/G	0.1579	likely_benign	0.1548	benign	-1.45	Destabilizing	0.642	D	0.371	neutral	N	0.502235205	None	None	N
V/H	0.3647	ambiguous	0.374	ambiguous	-0.861	Destabilizing	0.944	D	0.386	neutral	None	None	None	None	N
V/I	0.0836	likely_benign	0.0865	benign	-0.391	Destabilizing	0.329	N	0.233	neutral	None	None	None	None	N
V/K	0.1944	likely_benign	0.1968	benign	-0.977	Destabilizing	0.031	N	0.191	neutral	None	None	None	None	N
V/L	0.1257	likely_benign	0.133	benign	-0.391	Destabilizing	0.002	N	0.072	neutral	N	0.456790917	None	None	N
V/M	0.1272	likely_benign	0.1316	benign	-0.381	Destabilizing	0.139	N	0.127	neutral	N	0.485225484	None	None	N
V/N	0.1791	likely_benign	0.1867	benign	-0.854	Destabilizing	0.704	D	0.477	neutral	None	None	None	None	N
V/P	0.6018	likely_pathogenic	0.6494	pathogenic	-0.605	Destabilizing	0.828	D	0.471	neutral	None	None	None	None	N
V/Q	0.144	likely_benign	0.1453	benign	-0.961	Destabilizing	0.543	D	0.442	neutral	None	None	None	None	N
V/R	0.1889	likely_benign	0.1937	benign	-0.5	Destabilizing	0.543	D	0.477	neutral	None	None	None	None	N
V/S	0.1471	likely_benign	0.1537	benign	-1.378	Destabilizing	0.085	N	0.197	neutral	None	None	None	None	N
V/T	0.1352	likely_benign	0.1488	benign	-1.245	Destabilizing	0.031	N	0.091	neutral	None	None	None	None	N
V/W	0.6943	likely_pathogenic	0.6976	pathogenic	-0.98	Destabilizing	0.995	D	0.395	neutral	None	None	None	None	N
V/Y	0.4273	ambiguous	0.4514	ambiguous	-0.661	Destabilizing	0.981	D	0.364	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.