TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7201	21826;21827;21828	chr2:178723499;178723498;178723497	chr2:179588226;179588225;179588224
N2AB	6884	20875;20876;20877	chr2:178723499;178723498;178723497	chr2:179588226;179588225;179588224
N2A	5957	18094;18095;18096	chr2:178723499;178723498;178723497	chr2:179588226;179588225;179588224
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: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-56
• Domain position: 65
• Structural Position: 146
• Q(SASA): 0.9793
• 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
I/M	None	None	0.108	N	0.205	0.022	0.12205267543	gnomAD-4.0.0	2.05328E-06	None	None	None	None	I	None	5.97943E-05	0	None	0	0	None	0	0	0	0	1.65788E-05
I/V	rs755330865	0.035	None	N	0.121	0.035	0.126345400529	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
I/V	rs755330865	0.035	None	N	0.121	0.035	0.126345400529	gnomAD-4.0.0	4.1065E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	4.49802E-06	0	1.65782E-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
I/A	0.1052	likely_benign	0.1133	benign	-0.649	Destabilizing	0.002	N	0.201	neutral	None	None	None	None	I
I/C	0.4183	ambiguous	0.4408	ambiguous	-0.699	Destabilizing	0.245	N	0.171	neutral	None	None	None	None	I
I/D	0.2352	likely_benign	0.2768	benign	0.071	Stabilizing	0.018	N	0.232	neutral	None	None	None	None	I
I/E	0.2251	likely_benign	0.2604	benign	-0.012	Destabilizing	0.018	N	0.225	neutral	None	None	None	None	I
I/F	0.1013	likely_benign	0.1139	benign	-0.632	Destabilizing	None	N	0.183	neutral	None	None	None	None	I
I/G	0.2236	likely_benign	0.2609	benign	-0.816	Destabilizing	0.018	N	0.235	neutral	None	None	None	None	I
I/H	0.2119	likely_benign	0.2175	benign	-0.097	Destabilizing	0.497	N	0.201	neutral	None	None	None	None	I
I/K	0.1372	likely_benign	0.1487	benign	-0.292	Destabilizing	None	N	0.175	neutral	N	0.390444842	None	None	I
I/L	0.0866	likely_benign	0.0898	benign	-0.331	Destabilizing	None	N	0.121	neutral	N	0.407990452	None	None	I
I/M	0.0897	likely_benign	0.0937	benign	-0.378	Destabilizing	0.108	N	0.205	neutral	N	0.420479747	None	None	I
I/N	0.0928	likely_benign	0.1011	benign	-0.129	Destabilizing	0.044	N	0.311	neutral	None	None	None	None	I
I/P	0.1778	likely_benign	0.1764	benign	-0.403	Destabilizing	None	N	0.141	neutral	None	None	None	None	I
I/Q	0.1835	likely_benign	0.2012	benign	-0.329	Destabilizing	0.044	N	0.336	neutral	None	None	None	None	I
I/R	0.1082	likely_benign	0.1143	benign	0.222	Stabilizing	0.017	N	0.33	neutral	N	0.378803696	None	None	I
I/S	0.0906	likely_benign	0.0996	benign	-0.642	Destabilizing	None	N	0.105	neutral	None	None	None	None	I
I/T	0.0853	likely_benign	0.0902	benign	-0.612	Destabilizing	None	N	0.117	neutral	N	0.368512131	None	None	I
I/V	0.059	likely_benign	0.0625	benign	-0.403	Destabilizing	None	N	0.121	neutral	N	0.418458162	None	None	I
I/W	0.6019	likely_pathogenic	0.6026	pathogenic	-0.637	Destabilizing	0.788	D	0.177	neutral	None	None	None	None	I
I/Y	0.2765	likely_benign	0.2891	benign	-0.381	Destabilizing	0.022	N	0.281	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.