TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17135	51628;51629;51630	chr2:178610123;178610122;178610121	chr2:179474850;179474849;179474848
N2AB	15494	46705;46706;46707	chr2:178610123;178610122;178610121	chr2:179474850;179474849;179474848
N2A	14567	43924;43925;43926	chr2:178610123;178610122;178610121	chr2:179474850;179474849;179474848
N2B	8070	24433;24434;24435	chr2:178610123;178610122;178610121	chr2:179474850;179474849;179474848
Novex-1	8195	24808;24809;24810	chr2:178610123;178610122;178610121	chr2:179474850;179474849;179474848
Novex-2	8262	25009;25010;25011	chr2:178610123;178610122;178610121	chr2:179474850;179474849;179474848
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: Fn3-12
• Domain position: 89
• Structural Position: 123
• Q(SASA): 0.2221
• 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/P	rs756515794	-1.28	1.0	N	0.922	0.494	0.72014139575	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.62E-05	None	0	None	0	0	0
L/P	rs756515794	-1.28	1.0	N	0.922	0.494	0.72014139575	gnomAD-4.0.0	1.59318E-06	None	None	None	None	N	None	0	0	None	0	2.78505E-05	None	0	0	0	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	0.714	likely_pathogenic	0.7403	pathogenic	-2.072	Highly Destabilizing	0.998	D	0.831	deleterious	None	None	None	None	N
L/C	0.81	likely_pathogenic	0.8112	pathogenic	-1.199	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
L/D	0.9797	likely_pathogenic	0.9827	pathogenic	-1.951	Destabilizing	1.0	D	0.927	deleterious	None	None	None	None	N
L/E	0.8725	likely_pathogenic	0.9038	pathogenic	-1.829	Destabilizing	0.999	D	0.925	deleterious	None	None	None	None	N
L/F	0.5398	ambiguous	0.6668	pathogenic	-1.219	Destabilizing	0.999	D	0.799	deleterious	None	None	None	None	N
L/G	0.9218	likely_pathogenic	0.9271	pathogenic	-2.521	Highly Destabilizing	0.999	D	0.905	deleterious	None	None	None	None	N
L/H	0.8658	likely_pathogenic	0.9005	pathogenic	-1.882	Destabilizing	1.0	D	0.919	deleterious	None	None	None	None	N
L/I	0.1292	likely_benign	0.1775	benign	-0.837	Destabilizing	0.998	D	0.666	prob.neutral	None	None	None	None	N
L/K	0.8966	likely_pathogenic	0.9125	pathogenic	-1.602	Destabilizing	0.999	D	0.906	deleterious	None	None	None	None	N
L/M	0.1545	likely_benign	0.1852	benign	-0.648	Destabilizing	0.999	D	0.771	deleterious	N	0.50612558	None	None	N
L/N	0.8535	likely_pathogenic	0.88	pathogenic	-1.61	Destabilizing	1.0	D	0.931	deleterious	None	None	None	None	N
L/P	0.9531	likely_pathogenic	0.9579	pathogenic	-1.223	Destabilizing	1.0	D	0.922	deleterious	N	0.448133282	None	None	N
L/Q	0.6984	likely_pathogenic	0.7706	pathogenic	-1.629	Destabilizing	1.0	D	0.923	deleterious	N	0.469528225	None	None	N
L/R	0.8779	likely_pathogenic	0.8954	pathogenic	-1.16	Destabilizing	0.999	D	0.92	deleterious	N	0.464919869	None	None	N
L/S	0.8113	likely_pathogenic	0.8567	pathogenic	-2.252	Highly Destabilizing	0.999	D	0.883	deleterious	None	None	None	None	N
L/T	0.4489	ambiguous	0.4769	ambiguous	-2.005	Highly Destabilizing	0.999	D	0.891	deleterious	None	None	None	None	N
L/V	0.1674	likely_benign	0.2051	benign	-1.223	Destabilizing	0.997	D	0.661	prob.neutral	N	0.477994829	None	None	N
L/W	0.859	likely_pathogenic	0.8906	pathogenic	-1.5	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
L/Y	0.8789	likely_pathogenic	0.9137	pathogenic	-1.225	Destabilizing	0.999	D	0.858	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.