TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4997	15214;15215;15216	chr2:178734935;178734934;178734933	chr2:179599662;179599661;179599660
N2AB	4680	14263;14264;14265	chr2:178734935;178734934;178734933	chr2:179599662;179599661;179599660
N2A	3753	11482;11483;11484	chr2:178734935;178734934;178734933	chr2:179599662;179599661;179599660
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: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-33
• Domain position: 17
• Structural Position: 25
• Q(SASA): 0.4616
• 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
E/D	None	None	0.006	N	0.153	0.083	0.101711395817	gnomAD-4.0.0	1.60003E-06	None	None	None	None	I	None	0	0	None	0	2.79049E-05	None	0	0	0	0	0
E/G	rs775749900	-1.037	0.002	N	0.176	0.138	0.235664433957	gnomAD-2.1.1	2.08E-05	None	None	None	None	I	None	0	0	None	0	0	None	1.66456E-04	None	0	0	0
E/G	rs775749900	-1.037	0.002	N	0.176	0.138	0.235664433957	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	0	2.07125E-04	0
E/G	rs775749900	-1.037	0.002	N	0.176	0.138	0.235664433957	gnomAD-4.0.0	1.05588E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.87353E-04	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
E/A	0.3141	likely_benign	0.3419	ambiguous	-0.693	Destabilizing	0.01	N	0.159	neutral	N	0.457706861	None	None	I
E/C	0.9505	likely_pathogenic	0.9615	pathogenic	-0.239	Destabilizing	0.995	D	0.325	neutral	None	None	None	None	I
E/D	0.1595	likely_benign	0.1798	benign	-0.729	Destabilizing	0.006	N	0.153	neutral	N	0.438837634	None	None	I
E/F	0.8984	likely_pathogenic	0.9125	pathogenic	-0.257	Destabilizing	0.893	D	0.385	neutral	None	None	None	None	I
E/G	0.3185	likely_benign	0.3495	ambiguous	-0.991	Destabilizing	0.002	N	0.176	neutral	N	0.458012485	None	None	I
E/H	0.7162	likely_pathogenic	0.7573	pathogenic	-0.267	Destabilizing	0.981	D	0.278	neutral	None	None	None	None	I
E/I	0.707	likely_pathogenic	0.7261	pathogenic	0.096	Stabilizing	0.013	N	0.232	neutral	None	None	None	None	I
E/K	0.306	likely_benign	0.3168	benign	-0.018	Destabilizing	0.642	D	0.217	neutral	N	0.458083311	None	None	I
E/L	0.7237	likely_pathogenic	0.751	pathogenic	0.096	Stabilizing	0.329	N	0.37	neutral	None	None	None	None	I
E/M	0.6774	likely_pathogenic	0.6969	pathogenic	0.369	Stabilizing	0.176	N	0.279	neutral	None	None	None	None	I
E/N	0.395	ambiguous	0.4281	ambiguous	-0.563	Destabilizing	0.543	D	0.267	neutral	None	None	None	None	I
E/P	0.974	likely_pathogenic	0.9825	pathogenic	-0.145	Destabilizing	0.944	D	0.364	neutral	None	None	None	None	I
E/Q	0.2153	likely_benign	0.2349	benign	-0.462	Destabilizing	0.784	D	0.282	neutral	N	0.449348932	None	None	I
E/R	0.5317	ambiguous	0.5692	pathogenic	0.244	Stabilizing	0.828	D	0.273	neutral	None	None	None	None	I
E/S	0.3339	likely_benign	0.3702	ambiguous	-0.759	Destabilizing	0.329	N	0.227	neutral	None	None	None	None	I
E/T	0.4599	ambiguous	0.4953	ambiguous	-0.505	Destabilizing	0.704	D	0.304	neutral	None	None	None	None	I
E/V	0.474	ambiguous	0.4979	ambiguous	-0.145	Destabilizing	0.27	N	0.331	neutral	D	0.540370925	None	None	I
E/W	0.9748	likely_pathogenic	0.9817	pathogenic	0.012	Stabilizing	0.995	D	0.346	neutral	None	None	None	None	I
E/Y	0.8185	likely_pathogenic	0.8496	pathogenic	0.015	Stabilizing	0.981	D	0.331	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.