TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5094	15505;15506;15507	chr2:178734544;178734543;178734542	chr2:179599271;179599270;179599269
N2AB	4777	14554;14555;14556	chr2:178734544;178734543;178734542	chr2:179599271;179599270;179599269
N2A	3850	11773;11774;11775	chr2:178734544;178734543;178734542	chr2:179599271;179599270;179599269
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: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-34
• Domain position: 20
• Structural Position: 30
• Q(SASA): 0.0957
• 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	0.781	0.47	0.772391555924	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/R	None	None	1.0	D	0.903	0.877	0.922268766853	gnomAD-4.0.0	1.60397E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.44953E-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
L/A	0.9587	likely_pathogenic	0.9302	pathogenic	-2.771	Highly Destabilizing	0.999	D	0.754	deleterious	None	None	None	None	N
L/C	0.9405	likely_pathogenic	0.9112	pathogenic	-1.854	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
L/D	0.999	likely_pathogenic	0.9979	pathogenic	-3.392	Highly Destabilizing	1.0	D	0.908	deleterious	None	None	None	None	N
L/E	0.9928	likely_pathogenic	0.9848	pathogenic	-3.158	Highly Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
L/F	0.1948	likely_benign	0.1726	benign	-1.795	Destabilizing	1.0	D	0.781	deleterious	D	0.541062239	None	None	N
L/G	0.9914	likely_pathogenic	0.9825	pathogenic	-3.28	Highly Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
L/H	0.947	likely_pathogenic	0.8963	pathogenic	-2.657	Highly Destabilizing	1.0	D	0.877	deleterious	D	0.814917657	None	None	N
L/I	0.2349	likely_benign	0.2177	benign	-1.269	Destabilizing	0.999	D	0.574	neutral	D	0.623064247	None	None	N
L/K	0.9858	likely_pathogenic	0.9707	pathogenic	-2.236	Highly Destabilizing	1.0	D	0.906	deleterious	None	None	None	None	N
L/M	0.3028	likely_benign	0.2475	benign	-1.059	Destabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	N
L/N	0.9946	likely_pathogenic	0.9878	pathogenic	-2.614	Highly Destabilizing	1.0	D	0.909	deleterious	None	None	None	None	N
L/P	0.9949	likely_pathogenic	0.9914	pathogenic	-1.757	Destabilizing	1.0	D	0.906	deleterious	D	0.814917657	None	None	N
L/Q	0.9467	likely_pathogenic	0.8812	pathogenic	-2.509	Highly Destabilizing	1.0	D	0.915	deleterious	None	None	None	None	N
L/R	0.966	likely_pathogenic	0.9326	pathogenic	-1.911	Destabilizing	1.0	D	0.903	deleterious	D	0.814917657	None	None	N
L/S	0.9875	likely_pathogenic	0.9733	pathogenic	-3.212	Highly Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
L/T	0.9776	likely_pathogenic	0.9545	pathogenic	-2.841	Highly Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
L/V	0.3609	ambiguous	0.3017	benign	-1.757	Destabilizing	0.999	D	0.591	neutral	D	0.665077619	None	None	N
L/W	0.7589	likely_pathogenic	0.6903	pathogenic	-2.179	Highly Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
L/Y	0.8346	likely_pathogenic	0.7718	pathogenic	-1.907	Destabilizing	1.0	D	0.844	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.