TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9096	27511;27512;27513	chr2:178712739;178712738;178712737	chr2:179577466;179577465;179577464
N2AB	8779	26560;26561;26562	chr2:178712739;178712738;178712737	chr2:179577466;179577465;179577464
N2A	7852	23779;23780;23781	chr2:178712739;178712738;178712737	chr2:179577466;179577465;179577464
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-76
• Domain position: 78
• Structural Position: 162
• Q(SASA): 0.848
• 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	rs775382008	-0.03	0.001	N	0.137	0.097	0.151104730317	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
E/D	rs775382008	-0.03	0.001	N	0.137	0.097	0.151104730317	gnomAD-4.0.0	1.59138E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43287E-05	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	0.13	likely_benign	0.1367	benign	0.019	Stabilizing	0.016	N	0.209	neutral	N	0.465701189	None	None	I
E/C	0.8369	likely_pathogenic	0.8526	pathogenic	-0.097	Destabilizing	0.992	D	0.355	neutral	None	None	None	None	I
E/D	0.0853	likely_benign	0.0841	benign	-0.323	Destabilizing	0.001	N	0.137	neutral	N	0.422046412	None	None	I
E/F	0.6476	likely_pathogenic	0.6669	pathogenic	-0.109	Destabilizing	0.972	D	0.36	neutral	None	None	None	None	I
E/G	0.1544	likely_benign	0.1589	benign	-0.071	Destabilizing	0.334	N	0.359	neutral	N	0.494773302	None	None	I
E/H	0.3579	ambiguous	0.4029	ambiguous	0.455	Stabilizing	0.972	D	0.298	neutral	None	None	None	None	I
E/I	0.2718	likely_benign	0.2952	benign	0.195	Stabilizing	0.92	D	0.389	neutral	None	None	None	None	I
E/K	0.1162	likely_benign	0.1343	benign	0.435	Stabilizing	0.549	D	0.325	neutral	N	0.489346052	None	None	I
E/L	0.3278	likely_benign	0.3517	ambiguous	0.195	Stabilizing	0.617	D	0.372	neutral	None	None	None	None	I
E/M	0.3924	ambiguous	0.4267	ambiguous	0.03	Stabilizing	0.992	D	0.371	neutral	None	None	None	None	I
E/N	0.1952	likely_benign	0.2166	benign	0.287	Stabilizing	0.447	N	0.297	neutral	None	None	None	None	I
E/P	0.4759	ambiguous	0.4542	ambiguous	0.153	Stabilizing	0.92	D	0.37	neutral	None	None	None	None	I
E/Q	0.1416	likely_benign	0.1576	benign	0.278	Stabilizing	0.549	D	0.315	neutral	N	0.497293532	None	None	I
E/R	0.2077	likely_benign	0.2375	benign	0.592	Stabilizing	0.92	D	0.287	neutral	None	None	None	None	I
E/S	0.1697	likely_benign	0.1818	benign	0.142	Stabilizing	0.059	N	0.237	neutral	None	None	None	None	I
E/T	0.1904	likely_benign	0.2087	benign	0.223	Stabilizing	0.447	N	0.4	neutral	None	None	None	None	I
E/V	0.1661	likely_benign	0.1783	benign	0.153	Stabilizing	0.549	D	0.401	neutral	N	0.501757989	None	None	I
E/W	0.8305	likely_pathogenic	0.848	pathogenic	-0.099	Destabilizing	0.992	D	0.468	neutral	None	None	None	None	I
E/Y	0.5042	ambiguous	0.5267	ambiguous	0.105	Stabilizing	0.972	D	0.381	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.