TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9177	27754;27755;27756	chr2:178712393;178712392;178712391	chr2:179577120;179577119;179577118
N2AB	8860	26803;26804;26805	chr2:178712393;178712392;178712391	chr2:179577120;179577119;179577118
N2A	7933	24022;24023;24024	chr2:178712393;178712392;178712391	chr2:179577120;179577119;179577118
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-77
• Domain position: 66
• Structural Position: 148
• Q(SASA): 0.6297
• 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	rs1296040087	-0.495	0.722	N	0.433	0.172	0.299770980665	gnomAD-2.1.1	3.18E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
E/G	rs1296040087	-0.495	0.722	N	0.433	0.172	0.299770980665	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/G	rs1296040087	-0.495	0.722	N	0.433	0.172	0.299770980665	gnomAD-4.0.0	6.5716E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.4699E-05	0	0
E/K	None	None	0.722	N	0.483	0.212	0.234412748748	gnomAD-4.0.0	1.08029E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.18125E-05	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	0.1156	likely_benign	0.116	benign	-0.455	Destabilizing	0.722	D	0.438	neutral	N	0.514758132	None	None	N
E/C	0.8228	likely_pathogenic	0.7902	pathogenic	-0.012	Destabilizing	0.996	D	0.589	neutral	None	None	None	None	N
E/D	0.095	likely_benign	0.0955	benign	-0.303	Destabilizing	0.003	N	0.137	neutral	N	0.460462287	None	None	N
E/F	0.683	likely_pathogenic	0.6417	pathogenic	-0.367	Destabilizing	0.987	D	0.521	neutral	None	None	None	None	N
E/G	0.1306	likely_benign	0.1218	benign	-0.644	Destabilizing	0.722	D	0.433	neutral	N	0.516990361	None	None	N
E/H	0.4211	ambiguous	0.3771	ambiguous	-0.129	Destabilizing	0.961	D	0.412	neutral	None	None	None	None	N
E/I	0.3754	ambiguous	0.3447	ambiguous	0.01	Stabilizing	0.961	D	0.515	neutral	None	None	None	None	N
E/K	0.1385	likely_benign	0.119	benign	0.291	Stabilizing	0.722	D	0.483	neutral	N	0.504599854	None	None	N
E/L	0.3517	ambiguous	0.3271	benign	0.01	Stabilizing	0.961	D	0.439	neutral	None	None	None	None	N
E/M	0.4266	ambiguous	0.3939	ambiguous	0.184	Stabilizing	0.996	D	0.487	neutral	None	None	None	None	N
E/N	0.2133	likely_benign	0.1965	benign	-0.015	Destabilizing	0.044	N	0.228	neutral	None	None	None	None	N
E/P	0.6516	likely_pathogenic	0.62	pathogenic	-0.125	Destabilizing	0.961	D	0.399	neutral	None	None	None	None	N
E/Q	0.1433	likely_benign	0.1336	benign	0.024	Stabilizing	0.722	D	0.447	neutral	N	0.460886809	None	None	N
E/R	0.2242	likely_benign	0.1968	benign	0.481	Stabilizing	0.961	D	0.404	neutral	None	None	None	None	N
E/S	0.1645	likely_benign	0.1541	benign	-0.183	Destabilizing	0.633	D	0.458	neutral	None	None	None	None	N
E/T	0.1951	likely_benign	0.1799	benign	-0.025	Destabilizing	0.775	D	0.439	neutral	None	None	None	None	N
E/V	0.2301	likely_benign	0.2137	benign	-0.125	Destabilizing	0.949	D	0.405	neutral	N	0.482398105	None	None	N
E/W	0.8086	likely_pathogenic	0.7694	pathogenic	-0.219	Destabilizing	0.996	D	0.657	neutral	None	None	None	None	N
E/Y	0.5474	ambiguous	0.5063	ambiguous	-0.13	Destabilizing	0.987	D	0.487	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.