TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8005	24238;24239;24240	chr2:178719377;178719376;178719375	chr2:179584104;179584103;179584102
N2AB	7688	23287;23288;23289	chr2:178719377;178719376;178719375	chr2:179584104;179584103;179584102
N2A	6761	20506;20507;20508	chr2:178719377;178719376;178719375	chr2:179584104;179584103;179584102
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: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-65
• Domain position: 21
• Structural Position: 31
• Q(SASA): 0.4681
• 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
E/Q	rs757042397	-0.761	0.998	N	0.545	0.251	None	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	2.66E-05	0
E/Q	rs757042397	-0.761	0.998	N	0.545	0.251	None	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/Q	rs757042397	-0.761	0.998	N	0.545	0.251	None	gnomAD-4.0.0	2.97473E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.98397E-05	0	1.60113E-05

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	0.2534	likely_benign	0.3132	benign	-0.885	Destabilizing	0.835	D	0.502	neutral	N	0.500571489	None	None	N
E/C	0.9351	likely_pathogenic	0.9585	pathogenic	-0.548	Destabilizing	0.351	N	0.517	neutral	None	None	None	None	N
E/D	0.2042	likely_benign	0.253	benign	-1.195	Destabilizing	0.98	D	0.431	neutral	N	0.496869457	None	None	N
E/F	0.8742	likely_pathogenic	0.9168	pathogenic	-0.298	Destabilizing	0.999	D	0.722	prob.delet.	None	None	None	None	N
E/G	0.3093	likely_benign	0.3837	ambiguous	-1.26	Destabilizing	0.071	N	0.445	neutral	D	0.52217169	None	None	N
E/H	0.6141	likely_pathogenic	0.6791	pathogenic	-0.595	Destabilizing	1.0	D	0.566	neutral	None	None	None	None	N
E/I	0.5737	likely_pathogenic	0.6917	pathogenic	0.143	Stabilizing	0.996	D	0.714	prob.delet.	None	None	None	None	N
E/K	0.3646	ambiguous	0.4139	ambiguous	-0.792	Destabilizing	0.98	D	0.472	neutral	N	0.514761785	None	None	N
E/L	0.6111	likely_pathogenic	0.7327	pathogenic	0.143	Stabilizing	0.991	D	0.642	neutral	None	None	None	None	N
E/M	0.6664	likely_pathogenic	0.7566	pathogenic	0.582	Stabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	N
E/N	0.4026	ambiguous	0.4882	ambiguous	-1.257	Destabilizing	0.996	D	0.521	neutral	None	None	None	None	N
E/P	0.9182	likely_pathogenic	0.94	pathogenic	-0.178	Destabilizing	0.999	D	0.669	neutral	None	None	None	None	N
E/Q	0.1759	likely_benign	0.2008	benign	-1.107	Destabilizing	0.998	D	0.545	neutral	N	0.511606837	None	None	N
E/R	0.4883	ambiguous	0.5544	ambiguous	-0.488	Destabilizing	0.999	D	0.556	neutral	None	None	None	None	N
E/S	0.2816	likely_benign	0.3345	benign	-1.574	Destabilizing	0.97	D	0.403	neutral	None	None	None	None	N
E/T	0.3465	ambiguous	0.4201	ambiguous	-1.265	Destabilizing	0.996	D	0.616	neutral	None	None	None	None	N
E/V	0.3527	ambiguous	0.4495	ambiguous	-0.178	Destabilizing	0.989	D	0.625	neutral	N	0.495927134	None	None	N
E/W	0.9568	likely_pathogenic	0.9727	pathogenic	-0.061	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	N
E/Y	0.7902	likely_pathogenic	0.856	pathogenic	-0.062	Destabilizing	0.999	D	0.708	prob.delet.	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.