TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28005	84238;84239;84240	chr2:178562119;178562118;178562117	chr2:179426846;179426845;179426844
N2AB	26364	79315;79316;79317	chr2:178562119;178562118;178562117	chr2:179426846;179426845;179426844
N2A	25437	76534;76535;76536	chr2:178562119;178562118;178562117	chr2:179426846;179426845;179426844
N2B	18940	57043;57044;57045	chr2:178562119;178562118;178562117	chr2:179426846;179426845;179426844
Novex-1	19065	57418;57419;57420	chr2:178562119;178562118;178562117	chr2:179426846;179426845;179426844
Novex-2	19132	57619;57620;57621	chr2:178562119;178562118;178562117	chr2:179426846;179426845;179426844
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-142
• Domain position: 43
• Structural Position: 70
• Q(SASA): 0.4954
• 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/G	None	None	0.684	N	0.415	0.396	0.564094393547	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31251E-06	0	0
E/Q	rs1451115384	0.046	0.012	N	0.179	0.057	0.210429274316	gnomAD-2.1.1	4.06E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.99E-06	0
E/Q	rs1451115384	0.046	0.012	N	0.179	0.057	0.210429274316	gnomAD-4.0.0	1.59284E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86022E-06	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
E/A	0.1825	likely_benign	0.1949	benign	-0.483	Destabilizing	0.472	N	0.407	neutral	D	0.533251545	None	None	N
E/C	0.9115	likely_pathogenic	0.9191	pathogenic	-0.185	Destabilizing	0.996	D	0.508	neutral	None	None	None	None	N
E/D	0.3321	likely_benign	0.3168	benign	-0.545	Destabilizing	0.684	D	0.404	neutral	D	0.526672289	None	None	N
E/F	0.9007	likely_pathogenic	0.8913	pathogenic	-0.19	Destabilizing	0.984	D	0.467	neutral	None	None	None	None	N
E/G	0.2237	likely_benign	0.2367	benign	-0.731	Destabilizing	0.684	D	0.415	neutral	N	0.494343745	None	None	N
E/H	0.7438	likely_pathogenic	0.7547	pathogenic	-0.062	Destabilizing	0.953	D	0.397	neutral	None	None	None	None	N
E/I	0.5406	ambiguous	0.489	ambiguous	0.153	Stabilizing	0.953	D	0.461	neutral	None	None	None	None	N
E/K	0.2825	likely_benign	0.2867	benign	0.105	Stabilizing	0.309	N	0.437	neutral	N	0.500963109	None	None	N
E/L	0.5505	ambiguous	0.5234	ambiguous	0.153	Stabilizing	0.742	D	0.431	neutral	None	None	None	None	N
E/M	0.5518	ambiguous	0.5301	ambiguous	0.264	Stabilizing	0.984	D	0.447	neutral	None	None	None	None	N
E/N	0.4739	ambiguous	0.4646	ambiguous	-0.343	Destabilizing	0.742	D	0.387	neutral	None	None	None	None	N
E/P	0.451	ambiguous	0.4861	ambiguous	-0.038	Destabilizing	0.953	D	0.404	neutral	None	None	None	None	N
E/Q	0.1631	likely_benign	0.1671	benign	-0.257	Destabilizing	0.012	N	0.179	neutral	N	0.470760292	None	None	N
E/R	0.458	ambiguous	0.4714	ambiguous	0.36	Stabilizing	0.009	N	0.262	neutral	None	None	None	None	N
E/S	0.3588	ambiguous	0.3749	ambiguous	-0.494	Destabilizing	0.742	D	0.394	neutral	None	None	None	None	N
E/T	0.3641	ambiguous	0.3617	ambiguous	-0.287	Destabilizing	0.742	D	0.411	neutral	None	None	None	None	N
E/V	0.2952	likely_benign	0.2757	benign	-0.038	Destabilizing	0.939	D	0.411	neutral	N	0.518399523	None	None	N
E/W	0.9664	likely_pathogenic	0.9641	pathogenic	0.007	Stabilizing	0.996	D	0.556	neutral	None	None	None	None	N
E/Y	0.8062	likely_pathogenic	0.7981	pathogenic	0.056	Stabilizing	0.984	D	0.447	neutral	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.