TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14342	43249;43250;43251	chr2:178633249;178633248;178633247	chr2:179497976;179497975;179497974
N2AB	12701	38326;38327;38328	chr2:178633249;178633248;178633247	chr2:179497976;179497975;179497974
N2A	11774	35545;35546;35547	chr2:178633249;178633248;178633247	chr2:179497976;179497975;179497974
N2B	5277	16054;16055;16056	chr2:178633249;178633248;178633247	chr2:179497976;179497975;179497974
Novex-1	5402	16429;16430;16431	chr2:178633249;178633248;178633247	chr2:179497976;179497975;179497974
Novex-2	5469	16630;16631;16632	chr2:178633249;178633248;178633247	chr2:179497976;179497975;179497974
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-94
• Domain position: 24
• Structural Position: 35
• Q(SASA): 0.1024
• 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	rs1055213360	-2.405	0.994	N	0.901	0.44	0.522770035047	gnomAD-2.1.1	8.06E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
L/P	rs1055213360	-2.405	0.994	N	0.901	0.44	0.522770035047	gnomAD-4.0.0	1.09508E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.43947E-05	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	0.9447	likely_pathogenic	0.9317	pathogenic	-2.935	Highly Destabilizing	0.904	D	0.611	neutral	None	None	None	None	N
L/C	0.9495	likely_pathogenic	0.9512	pathogenic	-2.424	Highly Destabilizing	0.999	D	0.741	deleterious	None	None	None	None	N
L/D	0.9983	likely_pathogenic	0.998	pathogenic	-3.608	Highly Destabilizing	0.995	D	0.901	deleterious	None	None	None	None	N
L/E	0.993	likely_pathogenic	0.9914	pathogenic	-3.374	Highly Destabilizing	0.995	D	0.903	deleterious	None	None	None	None	N
L/F	0.8146	likely_pathogenic	0.7653	pathogenic	-1.491	Destabilizing	0.961	D	0.698	prob.delet.	N	0.431491645	None	None	N
L/G	0.9898	likely_pathogenic	0.9859	pathogenic	-3.433	Highly Destabilizing	0.995	D	0.906	deleterious	None	None	None	None	N
L/H	0.9893	likely_pathogenic	0.987	pathogenic	-2.816	Highly Destabilizing	0.998	D	0.875	deleterious	N	0.491353115	None	None	N
L/I	0.1101	likely_benign	0.1462	benign	-1.454	Destabilizing	0.009	N	0.233	neutral	N	0.379184132	None	None	N
L/K	0.9905	likely_pathogenic	0.9866	pathogenic	-2.284	Highly Destabilizing	0.985	D	0.86	deleterious	None	None	None	None	N
L/M	0.4099	ambiguous	0.3692	ambiguous	-1.662	Destabilizing	0.971	D	0.691	prob.delet.	None	None	None	None	N
L/N	0.9896	likely_pathogenic	0.9869	pathogenic	-2.745	Highly Destabilizing	0.995	D	0.898	deleterious	None	None	None	None	N
L/P	0.9933	likely_pathogenic	0.9914	pathogenic	-1.938	Destabilizing	0.994	D	0.901	deleterious	N	0.490637047	None	None	N
L/Q	0.9867	likely_pathogenic	0.9807	pathogenic	-2.547	Highly Destabilizing	0.995	D	0.831	deleterious	None	None	None	None	N
L/R	0.9825	likely_pathogenic	0.9777	pathogenic	-1.99	Destabilizing	0.994	D	0.84	deleterious	N	0.490637047	None	None	N
L/S	0.9888	likely_pathogenic	0.9865	pathogenic	-3.312	Highly Destabilizing	0.985	D	0.836	deleterious	None	None	None	None	N
L/T	0.9139	likely_pathogenic	0.8834	pathogenic	-2.958	Highly Destabilizing	0.971	D	0.755	deleterious	None	None	None	None	N
L/V	0.1885	likely_benign	0.1987	benign	-1.938	Destabilizing	0.595	D	0.455	neutral	N	0.418052195	None	None	N
L/W	0.9799	likely_pathogenic	0.9727	pathogenic	-1.944	Destabilizing	0.999	D	0.801	deleterious	None	None	None	None	N
L/Y	0.9838	likely_pathogenic	0.9789	pathogenic	-1.838	Destabilizing	0.995	D	0.731	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.