TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1615	5068;5069;5070	chr2:178777021;178777020;178777019	chr2:179641748;179641747;179641746
N2AB	1615	5068;5069;5070	chr2:178777021;178777020;178777019	chr2:179641748;179641747;179641746
N2A	1615	5068;5069;5070	chr2:178777021;178777020;178777019	chr2:179641748;179641747;179641746
N2B	1569	4930;4931;4932	chr2:178777021;178777020;178777019	chr2:179641748;179641747;179641746
Novex-1	1569	4930;4931;4932	chr2:178777021;178777020;178777019	chr2:179641748;179641747;179641746
Novex-2	1569	4930;4931;4932	chr2:178777021;178777020;178777019	chr2:179641748;179641747;179641746
Novex-3	1615	5068;5069;5070	chr2:178777021;178777020;178777019	chr2:179641748;179641747;179641746

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-7
• Domain position: 60
• Structural Position: 138
• Q(SASA): 0.0572
• 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	rs777977684	-1.652	0.121	D	0.423	0.367	None	gnomAD-2.1.1	4E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.85E-06	0
L/F	rs777977684	-1.652	0.121	D	0.423	0.367	None	gnomAD-4.0.0	6.1572E-06	None	None	None	None	N	None	2.98775E-05	0	None	0	0	None	0	0	7.19453E-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	0.9699	likely_pathogenic	0.9523	pathogenic	-2.698	Highly Destabilizing	0.992	D	0.757	deleterious	None	None	None	None	N
L/C	0.9343	likely_pathogenic	0.9041	pathogenic	-2.062	Highly Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	N
L/D	0.9999	likely_pathogenic	0.9998	pathogenic	-3.633	Highly Destabilizing	0.999	D	0.873	deleterious	None	None	None	None	N
L/E	0.9985	likely_pathogenic	0.9975	pathogenic	-3.333	Highly Destabilizing	0.999	D	0.869	deleterious	None	None	None	None	N
L/F	0.4732	ambiguous	0.4072	ambiguous	-1.722	Destabilizing	0.121	N	0.423	neutral	D	0.572531298	None	None	N
L/G	0.9959	likely_pathogenic	0.9933	pathogenic	-3.255	Highly Destabilizing	0.999	D	0.857	deleterious	None	None	None	None	N
L/H	0.9954	likely_pathogenic	0.9925	pathogenic	-2.92	Highly Destabilizing	1.0	D	0.873	deleterious	D	0.717924593	None	None	N
L/I	0.2759	likely_benign	0.2229	benign	-1.018	Destabilizing	0.978	D	0.622	neutral	D	0.631228988	None	None	N
L/K	0.9971	likely_pathogenic	0.9954	pathogenic	-2.266	Highly Destabilizing	0.999	D	0.845	deleterious	None	None	None	None	N
L/M	0.347	ambiguous	0.2907	benign	-1.169	Destabilizing	0.999	D	0.633	neutral	None	None	None	None	N
L/N	0.999	likely_pathogenic	0.9984	pathogenic	-2.963	Highly Destabilizing	0.999	D	0.875	deleterious	None	None	None	None	N
L/P	0.9989	likely_pathogenic	0.9982	pathogenic	-1.571	Destabilizing	0.999	D	0.883	deleterious	D	0.775995996	None	None	N
L/Q	0.9936	likely_pathogenic	0.9884	pathogenic	-2.663	Highly Destabilizing	0.999	D	0.864	deleterious	None	None	None	None	N
L/R	0.9925	likely_pathogenic	0.988	pathogenic	-2.264	Highly Destabilizing	0.999	D	0.857	deleterious	D	0.775995996	None	None	N
L/S	0.9974	likely_pathogenic	0.9953	pathogenic	-3.463	Highly Destabilizing	0.999	D	0.824	deleterious	None	None	None	None	N
L/T	0.9892	likely_pathogenic	0.9815	pathogenic	-3.008	Highly Destabilizing	0.999	D	0.779	deleterious	None	None	None	None	N
L/V	0.2977	likely_benign	0.2404	benign	-1.571	Destabilizing	0.978	D	0.656	neutral	D	0.642952088	None	None	N
L/W	0.9607	likely_pathogenic	0.9365	pathogenic	-2.122	Highly Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
L/Y	0.9748	likely_pathogenic	0.9619	pathogenic	-1.899	Destabilizing	0.99	D	0.773	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.