TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8232	24919;24920;24921	chr2:178718412;178718411;178718410	chr2:179583139;179583138;179583137
N2AB	7915	23968;23969;23970	chr2:178718412;178718411;178718410	chr2:179583139;179583138;179583137
N2A	6988	21187;21188;21189	chr2:178718412;178718411;178718410	chr2:179583139;179583138;179583137
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-67
• Domain position: 62
• Structural Position: 143
• Q(SASA): 0.3189
• 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	0.027	N	0.375	0.085	0.165133752707	gnomAD-4.0.0	4.80129E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	6.17284E-04	3.9375E-06	0	0
E/Q	None	None	None	N	0.272	0.072	0.101711395817	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.1284	likely_benign	0.1183	benign	-0.561	Destabilizing	0.027	N	0.337	neutral	N	0.472004646	None	None	N
E/C	0.6829	likely_pathogenic	0.6757	pathogenic	-0.024	Destabilizing	0.935	D	0.433	neutral	None	None	None	None	N
E/D	0.0901	likely_benign	0.0704	benign	-0.372	Destabilizing	None	N	0.121	neutral	N	0.448740997	None	None	N
E/F	0.5833	likely_pathogenic	0.5603	ambiguous	-0.414	Destabilizing	0.791	D	0.429	neutral	None	None	None	None	N
E/G	0.122	likely_benign	0.109	benign	-0.786	Destabilizing	0.027	N	0.375	neutral	N	0.479295977	None	None	N
E/H	0.2473	likely_benign	0.2344	benign	-0.419	Destabilizing	0.38	N	0.362	neutral	None	None	None	None	N
E/I	0.3435	ambiguous	0.3356	benign	0.006	Stabilizing	0.555	D	0.444	neutral	None	None	None	None	N
E/K	0.1148	likely_benign	0.1147	benign	0.234	Stabilizing	0.027	N	0.303	neutral	N	0.475562239	None	None	N
E/L	0.3471	ambiguous	0.3201	benign	0.006	Stabilizing	0.149	N	0.429	neutral	None	None	None	None	N
E/M	0.4331	ambiguous	0.4175	ambiguous	0.277	Stabilizing	0.824	D	0.391	neutral	None	None	None	None	N
E/N	0.1328	likely_benign	0.1079	benign	-0.119	Destabilizing	None	N	0.099	neutral	None	None	None	None	N
E/P	0.5129	ambiguous	0.5045	ambiguous	-0.163	Destabilizing	0.555	D	0.39	neutral	None	None	None	None	N
E/Q	0.103	likely_benign	0.1021	benign	-0.062	Destabilizing	None	N	0.272	neutral	N	0.466252109	None	None	N
E/R	0.1691	likely_benign	0.1741	benign	0.344	Stabilizing	0.081	N	0.321	neutral	None	None	None	None	N
E/S	0.1203	likely_benign	0.1087	benign	-0.293	Destabilizing	0.002	N	0.169	neutral	None	None	None	None	N
E/T	0.1641	likely_benign	0.1513	benign	-0.103	Destabilizing	0.081	N	0.343	neutral	None	None	None	None	N
E/V	0.2153	likely_benign	0.2069	benign	-0.163	Destabilizing	0.117	N	0.388	neutral	N	0.455629662	None	None	N
E/W	0.7584	likely_pathogenic	0.749	pathogenic	-0.234	Destabilizing	0.935	D	0.539	neutral	None	None	None	None	N
E/Y	0.3992	ambiguous	0.3719	ambiguous	-0.17	Destabilizing	0.555	D	0.415	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.