TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8159	24700;24701;24702	chr2:178718725;178718724;178718723	chr2:179583452;179583451;179583450
N2AB	7842	23749;23750;23751	chr2:178718725;178718724;178718723	chr2:179583452;179583451;179583450
N2A	6915	20968;20969;20970	chr2:178718725;178718724;178718723	chr2:179583452;179583451;179583450
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: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-66
• Domain position: 82
• Structural Position: 166
• Q(SASA): 0.1341
• Predicted PPI site: I

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
A/S	None	None	0.454	N	0.499	0.298	0.276482976112	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
A/C	0.5468	ambiguous	0.5356	ambiguous	-0.762	Destabilizing	0.998	D	0.553	neutral	None	None	None	None	I
A/D	0.1961	likely_benign	0.2096	benign	-0.524	Destabilizing	0.012	N	0.484	neutral	N	0.480726569	None	None	I
A/E	0.2365	likely_benign	0.2297	benign	-0.577	Destabilizing	0.067	N	0.387	neutral	None	None	None	None	I
A/F	0.3332	likely_benign	0.31	benign	-0.881	Destabilizing	0.974	D	0.649	neutral	None	None	None	None	I
A/G	0.2132	likely_benign	0.2064	benign	-0.941	Destabilizing	0.801	D	0.497	neutral	N	0.498471575	None	None	I
A/H	0.4809	ambiguous	0.4604	ambiguous	-1.034	Destabilizing	0.998	D	0.6	neutral	None	None	None	None	I
A/I	0.1813	likely_benign	0.1768	benign	-0.263	Destabilizing	0.728	D	0.586	neutral	None	None	None	None	I
A/K	0.4067	ambiguous	0.3795	ambiguous	-0.893	Destabilizing	0.842	D	0.564	neutral	None	None	None	None	I
A/L	0.2071	likely_benign	0.2011	benign	-0.263	Destabilizing	0.728	D	0.539	neutral	None	None	None	None	I
A/M	0.2266	likely_benign	0.2217	benign	-0.257	Destabilizing	0.974	D	0.575	neutral	None	None	None	None	I
A/N	0.2409	likely_benign	0.2635	benign	-0.58	Destabilizing	0.904	D	0.641	neutral	None	None	None	None	I
A/P	0.9101	likely_pathogenic	0.8954	pathogenic	-0.371	Destabilizing	0.966	D	0.614	neutral	D	0.528350209	None	None	I
A/Q	0.3498	ambiguous	0.3251	benign	-0.74	Destabilizing	0.949	D	0.616	neutral	None	None	None	None	I
A/R	0.3644	ambiguous	0.3283	benign	-0.584	Destabilizing	0.949	D	0.61	neutral	None	None	None	None	I
A/S	0.0932	likely_benign	0.0968	benign	-0.98	Destabilizing	0.454	N	0.499	neutral	N	0.487645021	None	None	I
A/T	0.0765	likely_benign	0.0784	benign	-0.932	Destabilizing	0.051	N	0.409	neutral	N	0.49310275	None	None	I
A/V	0.1008	likely_benign	0.0987	benign	-0.371	Destabilizing	0.051	N	0.368	neutral	D	0.524573347	None	None	I
A/W	0.8217	likely_pathogenic	0.7769	pathogenic	-1.166	Destabilizing	0.998	D	0.681	prob.neutral	None	None	None	None	I
A/Y	0.49	ambiguous	0.4652	ambiguous	-0.759	Destabilizing	0.991	D	0.64	neutral	None	None	None	None	I

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.