TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9187	27784;27785;27786	chr2:178712363;178712362;178712361	chr2:179577090;179577089;179577088
N2AB	8870	26833;26834;26835	chr2:178712363;178712362;178712361	chr2:179577090;179577089;179577088
N2A	7943	24052;24053;24054	chr2:178712363;178712362;178712361	chr2:179577090;179577089;179577088
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: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-77
• Domain position: 76
• Structural Position: 159
• Q(SASA): 0.4278
• 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/D	rs796818398	-0.777	0.005	N	0.116	0.05	0.208816687407	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.87E-06	0
E/D	rs796818398	-0.777	0.005	N	0.116	0.05	0.208816687407	gnomAD-4.0.0	2.73685E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.59783E-06	0	0
E/K	rs1195527997	0.123	0.012	N	0.141	0.235	0.273938319068	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
E/K	rs1195527997	0.123	0.012	N	0.141	0.235	0.273938319068	gnomAD-4.0.0	1.59133E-06	None	None	None	None	N	None	0	2.28634E-05	None	0	0	None	0	0	0	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	0.1884	likely_benign	0.1992	benign	-0.709	Destabilizing	0.454	N	0.405	neutral	D	0.530923316	None	None	N
E/C	0.8842	likely_pathogenic	0.8903	pathogenic	-0.162	Destabilizing	0.998	D	0.549	neutral	None	None	None	None	N
E/D	0.2653	likely_benign	0.2429	benign	-0.877	Destabilizing	0.005	N	0.116	neutral	N	0.503603429	None	None	N
E/F	0.8226	likely_pathogenic	0.8312	pathogenic	-0.701	Destabilizing	0.991	D	0.535	neutral	None	None	None	None	N
E/G	0.2382	likely_benign	0.2431	benign	-0.983	Destabilizing	0.801	D	0.445	neutral	N	0.494584008	None	None	N
E/H	0.484	ambiguous	0.5207	ambiguous	-0.953	Destabilizing	0.991	D	0.481	neutral	None	None	None	None	N
E/I	0.4696	ambiguous	0.4811	ambiguous	0.01	Stabilizing	0.974	D	0.546	neutral	None	None	None	None	N
E/K	0.1628	likely_benign	0.1858	benign	-0.123	Destabilizing	0.012	N	0.141	neutral	N	0.479974421	None	None	N
E/L	0.5462	ambiguous	0.5525	ambiguous	0.01	Stabilizing	0.842	D	0.511	neutral	None	None	None	None	N
E/M	0.527	ambiguous	0.5431	ambiguous	0.449	Stabilizing	0.998	D	0.505	neutral	None	None	None	None	N
E/N	0.3982	ambiguous	0.3948	ambiguous	-0.433	Destabilizing	0.842	D	0.316	neutral	None	None	None	None	N
E/P	0.9878	likely_pathogenic	0.9856	pathogenic	-0.209	Destabilizing	0.974	D	0.427	neutral	None	None	None	None	N
E/Q	0.1217	likely_benign	0.129	benign	-0.395	Destabilizing	0.801	D	0.407	neutral	N	0.504160789	None	None	N
E/R	0.2813	likely_benign	0.309	benign	-0.077	Destabilizing	0.728	D	0.405	neutral	None	None	None	None	N
E/S	0.2195	likely_benign	0.2243	benign	-0.683	Destabilizing	0.08	N	0.11	neutral	None	None	None	None	N
E/T	0.2299	likely_benign	0.2436	benign	-0.456	Destabilizing	0.728	D	0.381	neutral	None	None	None	None	N
E/V	0.2848	likely_benign	0.2835	benign	-0.209	Destabilizing	0.891	D	0.475	neutral	D	0.52228519	None	None	N
E/W	0.9157	likely_pathogenic	0.9234	pathogenic	-0.574	Destabilizing	0.998	D	0.637	neutral	None	None	None	None	N
E/Y	0.7289	likely_pathogenic	0.7404	pathogenic	-0.455	Destabilizing	0.991	D	0.514	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.