TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5660	17203;17204;17205	chr2:178731897;178731896;178731895	chr2:179596624;179596623;179596622
N2AB	5343	16252;16253;16254	chr2:178731897;178731896;178731895	chr2:179596624;179596623;179596622
N2A	4416	13471;13472;13473	chr2:178731897;178731896;178731895	chr2:179596624;179596623;179596622
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-40
• Domain position: 24
• Structural Position: 35
• Q(SASA): 0.0986
• 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	None	None	0.217	D	0.292	0.328	0.469415673434	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-05	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	0.3004	likely_benign	0.3689	ambiguous	-1.908	Destabilizing	0.994	D	0.664	neutral	N	0.498936689	None	None	N
V/C	0.9179	likely_pathogenic	0.9222	pathogenic	-1.202	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
V/D	0.9701	likely_pathogenic	0.9801	pathogenic	-2.708	Highly Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
V/E	0.9235	likely_pathogenic	0.9485	pathogenic	-2.409	Highly Destabilizing	0.999	D	0.831	deleterious	D	0.565334783	None	None	N
V/F	0.3951	ambiguous	0.392	ambiguous	-1.059	Destabilizing	0.998	D	0.816	deleterious	None	None	None	None	N
V/G	0.5984	likely_pathogenic	0.6449	pathogenic	-2.506	Highly Destabilizing	0.999	D	0.852	deleterious	D	0.557441185	None	None	N
V/H	0.974	likely_pathogenic	0.9812	pathogenic	-2.472	Highly Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
V/I	0.0937	likely_benign	0.1	benign	-0.191	Destabilizing	0.611	D	0.24	neutral	None	None	None	None	N
V/K	0.9438	likely_pathogenic	0.9636	pathogenic	-1.429	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
V/L	0.3036	likely_benign	0.3309	benign	-0.191	Destabilizing	0.217	N	0.292	neutral	D	0.545858861	None	None	N
V/M	0.2804	likely_benign	0.3113	benign	-0.307	Destabilizing	0.997	D	0.726	prob.delet.	D	0.56075221	None	None	N
V/N	0.927	likely_pathogenic	0.9471	pathogenic	-1.991	Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
V/P	0.941	likely_pathogenic	0.9614	pathogenic	-0.741	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
V/Q	0.9339	likely_pathogenic	0.9536	pathogenic	-1.669	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
V/R	0.9227	likely_pathogenic	0.945	pathogenic	-1.572	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
V/S	0.7653	likely_pathogenic	0.8125	pathogenic	-2.544	Highly Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
V/T	0.4538	ambiguous	0.5266	ambiguous	-2.087	Highly Destabilizing	0.996	D	0.709	prob.delet.	None	None	None	None	N
V/W	0.9669	likely_pathogenic	0.9727	pathogenic	-1.679	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
V/Y	0.8841	likely_pathogenic	0.8914	pathogenic	-1.249	Destabilizing	1.0	D	0.795	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.