TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26623	80092;80093;80094	chr2:178566265;178566264;178566263	chr2:179430992;179430991;179430990
N2AB	24982	75169;75170;75171	chr2:178566265;178566264;178566263	chr2:179430992;179430991;179430990
N2A	24055	72388;72389;72390	chr2:178566265;178566264;178566263	chr2:179430992;179430991;179430990
N2B	17558	52897;52898;52899	chr2:178566265;178566264;178566263	chr2:179430992;179430991;179430990
Novex-1	17683	53272;53273;53274	chr2:178566265;178566264;178566263	chr2:179430992;179430991;179430990
Novex-2	17750	53473;53474;53475	chr2:178566265;178566264;178566263	chr2:179430992;179430991;179430990
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-138
• Domain position: 30
• Structural Position: 45
• Q(SASA): 0.7081
• 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
E/D	rs751704572	None	0.001	N	0.177	0.08	0.165133752707	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
E/D	rs751704572	None	0.001	N	0.177	0.08	0.165133752707	gnomAD-4.0.0	6.5735E-06	None	None	None	None	I	None	2.41324E-05	0	None	0	0	None	0	0	0	0	0
E/K	rs1705804390	None	0.003	N	0.293	0.179	0.340273420219	gnomAD-4.0.0	2.737E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.59809E-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	0.1265	likely_benign	0.1236	benign	-0.502	Destabilizing	0.338	N	0.575	neutral	D	0.533944978	None	None	I
E/C	0.692	likely_pathogenic	0.6431	pathogenic	-0.293	Destabilizing	0.991	D	0.724	prob.delet.	None	None	None	None	I
E/D	0.0796	likely_benign	0.0737	benign	-0.594	Destabilizing	0.001	N	0.177	neutral	N	0.518071449	None	None	I
E/F	0.6131	likely_pathogenic	0.6016	pathogenic	-0.109	Destabilizing	0.967	D	0.673	neutral	None	None	None	None	I
E/G	0.1651	likely_benign	0.1611	benign	-0.772	Destabilizing	0.505	D	0.603	neutral	N	0.511144553	None	None	I
E/H	0.3089	likely_benign	0.2955	benign	-0.002	Destabilizing	0.906	D	0.585	neutral	None	None	None	None	I
E/I	0.2002	likely_benign	0.1994	benign	0.199	Stabilizing	0.906	D	0.677	prob.neutral	None	None	None	None	I
E/K	0.1344	likely_benign	0.1358	benign	-0.028	Destabilizing	0.003	N	0.293	neutral	N	0.481457288	None	None	I
E/L	0.261	likely_benign	0.2561	benign	0.199	Stabilizing	0.826	D	0.609	neutral	None	None	None	None	I
E/M	0.3206	likely_benign	0.32	benign	0.277	Stabilizing	0.991	D	0.672	neutral	None	None	None	None	I
E/N	0.1137	likely_benign	0.1075	benign	-0.48	Destabilizing	0.404	N	0.561	neutral	None	None	None	None	I
E/P	0.8468	likely_pathogenic	0.8441	pathogenic	-0.014	Destabilizing	0.906	D	0.615	neutral	None	None	None	None	I
E/Q	0.1165	likely_benign	0.1203	benign	-0.39	Destabilizing	0.084	N	0.275	neutral	N	0.496445383	None	None	I
E/R	0.2308	likely_benign	0.237	benign	0.287	Stabilizing	0.404	N	0.551	neutral	None	None	None	None	I
E/S	0.1268	likely_benign	0.1234	benign	-0.663	Destabilizing	0.404	N	0.536	neutral	None	None	None	None	I
E/T	0.1404	likely_benign	0.1391	benign	-0.441	Destabilizing	0.575	D	0.594	neutral	None	None	None	None	I
E/V	0.1362	likely_benign	0.1348	benign	-0.014	Destabilizing	0.782	D	0.615	neutral	N	0.506817092	None	None	I
E/W	0.8426	likely_pathogenic	0.8266	pathogenic	0.109	Stabilizing	0.991	D	0.717	prob.delet.	None	None	None	None	I
E/Y	0.4492	ambiguous	0.417	ambiguous	0.139	Stabilizing	0.967	D	0.681	prob.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.