TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5280	16063;16064;16065	chr2:178733455;178733454;178733453	chr2:179598182;179598181;179598180
N2AB	4963	15112;15113;15114	chr2:178733455;178733454;178733453	chr2:179598182;179598181;179598180
N2A	4036	12331;12332;12333	chr2:178733455;178733454;178733453	chr2:179598182;179598181;179598180
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: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-36
• Domain position: 20
• Structural Position: 30
• Q(SASA): 0.1405
• 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
L/V	rs879207679	None	0.996	D	0.693	0.522	0.675152924593	gnomAD-4.0.0	1.59133E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85838E-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
L/A	0.841	likely_pathogenic	0.8505	pathogenic	-1.978	Destabilizing	0.998	D	0.742	deleterious	None	None	None	None	N
L/C	0.9078	likely_pathogenic	0.9104	pathogenic	-1.267	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
L/D	0.9983	likely_pathogenic	0.9982	pathogenic	-2.796	Highly Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
L/E	0.9862	likely_pathogenic	0.9851	pathogenic	-2.505	Highly Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
L/F	0.2807	likely_benign	0.2789	benign	-1.284	Destabilizing	0.702	D	0.479	neutral	None	None	None	None	N
L/G	0.9836	likely_pathogenic	0.9813	pathogenic	-2.497	Highly Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
L/H	0.9581	likely_pathogenic	0.9557	pathogenic	-2.458	Highly Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
L/I	0.1358	likely_benign	0.1419	benign	-0.416	Destabilizing	0.997	D	0.675	neutral	None	None	None	None	N
L/K	0.9784	likely_pathogenic	0.9741	pathogenic	-1.518	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
L/M	0.1788	likely_benign	0.1939	benign	-0.673	Destabilizing	1.0	D	0.765	deleterious	D	0.691089312	None	None	N
L/N	0.9912	likely_pathogenic	0.9899	pathogenic	-2.235	Highly Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
L/P	0.9924	likely_pathogenic	0.9935	pathogenic	-0.929	Destabilizing	1.0	D	0.871	deleterious	D	0.842288788	None	None	N
L/Q	0.9424	likely_pathogenic	0.9394	pathogenic	-1.834	Destabilizing	1.0	D	0.86	deleterious	D	0.842288788	None	None	N
L/R	0.9584	likely_pathogenic	0.955	pathogenic	-1.872	Destabilizing	1.0	D	0.846	deleterious	D	0.842288788	None	None	N
L/S	0.9698	likely_pathogenic	0.97	pathogenic	-2.622	Highly Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
L/T	0.8976	likely_pathogenic	0.9014	pathogenic	-2.174	Highly Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
L/V	0.1702	likely_benign	0.1916	benign	-0.929	Destabilizing	0.996	D	0.693	prob.neutral	D	0.707335855	None	None	N
L/W	0.7748	likely_pathogenic	0.7647	pathogenic	-1.614	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
L/Y	0.8895	likely_pathogenic	0.8735	pathogenic	-1.388	Destabilizing	0.998	D	0.818	deleterious	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.