TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8108	24547;24548;24549	chr2:178718878;178718877;178718876	chr2:179583605;179583604;179583603
N2AB	7791	23596;23597;23598	chr2:178718878;178718877;178718876	chr2:179583605;179583604;179583603
N2A	6864	20815;20816;20817	chr2:178718878;178718877;178718876	chr2:179583605;179583604;179583603
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: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-66
• Domain position: 31
• Structural Position: 45
• Q(SASA): 0.4806
• 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
K/E	rs776437978	0.473	0.062	N	0.447	0.129	None	gnomAD-2.1.1	1.21E-05	None	None	None	None	I	None	1.94124E-04	0	None	0	0	None	0	None	0	0	0
K/E	rs776437978	0.473	0.062	N	0.447	0.129	None	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	2.42E-05	0	0	0	0	None	0	0	0	0	0
K/E	rs776437978	0.473	0.062	N	0.447	0.129	None	gnomAD-4.0.0	4.33856E-06	None	None	None	None	I	None	6.67913E-05	0	None	0	0	None	0	0	8.4768E-07	1.09818E-05	0
K/N	None	None	None	N	0.225	0.138	0.207176502487	gnomAD-4.0.0	6.8427E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99504E-07	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
K/A	0.2503	likely_benign	0.2313	benign	-0.077	Destabilizing	0.035	N	0.483	neutral	None	None	None	None	I
K/C	0.6556	likely_pathogenic	0.6288	pathogenic	-0.253	Destabilizing	0.824	D	0.551	neutral	None	None	None	None	I
K/D	0.3959	ambiguous	0.342	ambiguous	0.101	Stabilizing	0.081	N	0.549	neutral	None	None	None	None	I
K/E	0.1168	likely_benign	0.1097	benign	0.159	Stabilizing	0.062	N	0.447	neutral	N	0.468775992	None	None	I
K/F	0.6482	likely_pathogenic	0.6234	pathogenic	0.021	Stabilizing	0.38	N	0.573	neutral	None	None	None	None	I
K/G	0.4173	ambiguous	0.3725	ambiguous	-0.364	Destabilizing	0.081	N	0.531	neutral	None	None	None	None	I
K/H	0.1969	likely_benign	0.1821	benign	-0.64	Destabilizing	0.38	N	0.518	neutral	None	None	None	None	I
K/I	0.2564	likely_benign	0.2498	benign	0.622	Stabilizing	0.235	N	0.565	neutral	None	None	None	None	I
K/L	0.2696	likely_benign	0.2529	benign	0.622	Stabilizing	0.029	N	0.517	neutral	None	None	None	None	I
K/M	0.1809	likely_benign	0.1764	benign	0.285	Stabilizing	0.027	N	0.407	neutral	N	0.498204859	None	None	I
K/N	0.2595	likely_benign	0.2277	benign	0.018	Stabilizing	None	N	0.225	neutral	N	0.493655794	None	None	I
K/P	0.837	likely_pathogenic	0.8004	pathogenic	0.42	Stabilizing	0.555	D	0.552	neutral	None	None	None	None	I
K/Q	0.1006	likely_benign	0.0956	benign	-0.068	Destabilizing	0.001	N	0.228	neutral	N	0.469450783	None	None	I
K/R	0.0783	likely_benign	0.0777	benign	-0.266	Destabilizing	0.062	N	0.455	neutral	N	0.503987431	None	None	I
K/S	0.2519	likely_benign	0.2169	benign	-0.499	Destabilizing	0.035	N	0.422	neutral	None	None	None	None	I
K/T	0.1066	likely_benign	0.1016	benign	-0.264	Destabilizing	None	N	0.249	neutral	N	0.439725309	None	None	I
K/V	0.2407	likely_benign	0.2332	benign	0.42	Stabilizing	0.081	N	0.531	neutral	None	None	None	None	I
K/W	0.661	likely_pathogenic	0.6511	pathogenic	0.041	Stabilizing	0.935	D	0.597	neutral	None	None	None	None	I
K/Y	0.5047	ambiguous	0.4756	ambiguous	0.354	Stabilizing	0.555	D	0.575	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.