TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32980	99163;99164;99165	chr2:178538997;178538996;178538995	chr2:179403724;179403723;179403722
N2AB	31339	94240;94241;94242	chr2:178538997;178538996;178538995	chr2:179403724;179403723;179403722
N2A	30412	91459;91460;91461	chr2:178538997;178538996;178538995	chr2:179403724;179403723;179403722
N2B	23915	71968;71969;71970	chr2:178538997;178538996;178538995	chr2:179403724;179403723;179403722
Novex-1	24040	72343;72344;72345	chr2:178538997;178538996;178538995	chr2:179403724;179403723;179403722
Novex-2	24107	72544;72545;72546	chr2:178538997;178538996;178538995	chr2:179403724;179403723;179403722
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: Fn3-128
• Domain position: 85
• Structural Position: 117
• Q(SASA): 0.3636
• 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	None	None	0.966	N	0.688	0.319	0.776386403144	gnomAD-4.0.0	4.77789E-06	None	None	None	None	N	None	0	2.28697E-05	None	0	0	None	0	0	5.72384E-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	0.3192	likely_benign	0.3122	benign	-1.587	Destabilizing	0.688	D	0.493	neutral	None	None	None	None	N
L/C	0.6534	likely_pathogenic	0.6137	pathogenic	-0.955	Destabilizing	0.998	D	0.604	neutral	None	None	None	None	N
L/D	0.718	likely_pathogenic	0.6702	pathogenic	-0.756	Destabilizing	0.728	D	0.635	neutral	None	None	None	None	N
L/E	0.3088	likely_benign	0.2554	benign	-0.773	Destabilizing	0.016	N	0.472	neutral	None	None	None	None	N
L/F	0.1894	likely_benign	0.2002	benign	-1.149	Destabilizing	0.991	D	0.606	neutral	None	None	None	None	N
L/G	0.7057	likely_pathogenic	0.6988	pathogenic	-1.887	Destabilizing	0.842	D	0.652	neutral	None	None	None	None	N
L/H	0.3855	ambiguous	0.3559	ambiguous	-0.966	Destabilizing	0.974	D	0.677	prob.neutral	None	None	None	None	N
L/I	0.1025	likely_benign	0.0989	benign	-0.851	Destabilizing	0.915	D	0.49	neutral	None	None	None	None	N
L/K	0.3558	ambiguous	0.3045	benign	-0.915	Destabilizing	0.728	D	0.605	neutral	None	None	None	None	N
L/M	0.1299	likely_benign	0.1297	benign	-0.655	Destabilizing	0.989	D	0.611	neutral	N	0.450333799	None	None	N
L/N	0.4213	ambiguous	0.4248	ambiguous	-0.682	Destabilizing	0.949	D	0.665	neutral	None	None	None	None	N
L/P	0.3616	ambiguous	0.3997	ambiguous	-1.064	Destabilizing	0.966	D	0.688	prob.neutral	N	0.435980422	None	None	N
L/Q	0.1816	likely_benign	0.1683	benign	-0.902	Destabilizing	0.136	N	0.433	neutral	N	0.418509382	None	None	N
L/R	0.3655	ambiguous	0.3242	benign	-0.285	Destabilizing	0.801	D	0.655	neutral	N	0.409871256	None	None	N
L/S	0.3841	ambiguous	0.3671	ambiguous	-1.345	Destabilizing	0.842	D	0.604	neutral	None	None	None	None	N
L/T	0.2722	likely_benign	0.2475	benign	-1.246	Destabilizing	0.842	D	0.574	neutral	None	None	None	None	N
L/V	0.1124	likely_benign	0.1088	benign	-1.064	Destabilizing	0.891	D	0.449	neutral	N	0.423800559	None	None	N
L/W	0.4213	ambiguous	0.4117	ambiguous	-1.135	Destabilizing	0.998	D	0.691	prob.neutral	None	None	None	None	N
L/Y	0.4531	ambiguous	0.4639	ambiguous	-0.932	Destabilizing	0.991	D	0.62	neutral	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.