TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15159	45700;45701;45702	chr2:178621243;178621242;178621241	chr2:179485970;179485969;179485968
N2AB	13518	40777;40778;40779	chr2:178621243;178621242;178621241	chr2:179485970;179485969;179485968
N2A	12591	37996;37997;37998	chr2:178621243;178621242;178621241	chr2:179485970;179485969;179485968
N2B	6094	18505;18506;18507	chr2:178621243;178621242;178621241	chr2:179485970;179485969;179485968
Novex-1	6219	18880;18881;18882	chr2:178621243;178621242;178621241	chr2:179485970;179485969;179485968
Novex-2	6286	19081;19082;19083	chr2:178621243;178621242;178621241	chr2:179485970;179485969;179485968
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-103
• Domain position: 40
• Structural Position: 58
• Q(SASA): 0.1646
• 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/F	None	None	1.0	D	0.735	0.543	0.795952509824	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
L/P	None	None	0.999	D	0.863	0.789	0.865169967319	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
L/V	None	None	0.996	D	0.501	0.392	0.69744551405	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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	0.8061	likely_pathogenic	0.7679	pathogenic	-2.276	Highly Destabilizing	0.813	D	0.403	neutral	None	None	None	None	N
L/C	0.9268	likely_pathogenic	0.8927	pathogenic	-1.539	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
L/D	0.9959	likely_pathogenic	0.9953	pathogenic	-2.07	Highly Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	N
L/E	0.9498	likely_pathogenic	0.9405	pathogenic	-1.871	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
L/F	0.4919	ambiguous	0.4438	ambiguous	-1.324	Destabilizing	1.0	D	0.735	prob.delet.	D	0.709116658	None	None	N
L/G	0.9788	likely_pathogenic	0.9706	pathogenic	-2.775	Highly Destabilizing	0.999	D	0.797	deleterious	None	None	None	None	N
L/H	0.9377	likely_pathogenic	0.9197	pathogenic	-1.898	Destabilizing	1.0	D	0.849	deleterious	D	0.769261733	None	None	N
L/I	0.084	likely_benign	0.0895	benign	-0.859	Destabilizing	0.998	D	0.507	neutral	N	0.501487821	None	None	N
L/K	0.9322	likely_pathogenic	0.9132	pathogenic	-1.686	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
L/M	0.2391	likely_benign	0.2351	benign	-0.812	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
L/N	0.9801	likely_pathogenic	0.9774	pathogenic	-1.935	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
L/P	0.9624	likely_pathogenic	0.9505	pathogenic	-1.31	Destabilizing	0.999	D	0.863	deleterious	D	0.732430227	None	None	N
L/Q	0.8724	likely_pathogenic	0.8451	pathogenic	-1.837	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
L/R	0.8973	likely_pathogenic	0.8633	pathogenic	-1.367	Destabilizing	0.999	D	0.847	deleterious	D	0.732430227	None	None	N
L/S	0.9572	likely_pathogenic	0.9499	pathogenic	-2.665	Highly Destabilizing	0.998	D	0.759	deleterious	None	None	None	None	N
L/T	0.8184	likely_pathogenic	0.7892	pathogenic	-2.311	Highly Destabilizing	0.999	D	0.725	prob.delet.	None	None	None	None	N
L/V	0.1238	likely_benign	0.1176	benign	-1.31	Destabilizing	0.996	D	0.501	neutral	D	0.542105616	None	None	N
L/W	0.8465	likely_pathogenic	0.7843	pathogenic	-1.528	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
L/Y	0.9132	likely_pathogenic	0.8859	pathogenic	-1.262	Destabilizing	1.0	D	0.835	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.