TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26629	80110;80111;80112	chr2:178566247;178566246;178566245	chr2:179430974;179430973;179430972
N2AB	24988	75187;75188;75189	chr2:178566247;178566246;178566245	chr2:179430974;179430973;179430972
N2A	24061	72406;72407;72408	chr2:178566247;178566246;178566245	chr2:179430974;179430973;179430972
N2B	17564	52915;52916;52917	chr2:178566247;178566246;178566245	chr2:179430974;179430973;179430972
Novex-1	17689	53290;53291;53292	chr2:178566247;178566246;178566245	chr2:179430974;179430973;179430972
Novex-2	17756	53491;53492;53493	chr2:178566247;178566246;178566245	chr2:179430974;179430973;179430972
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: 36
• Structural Position: 51
• Q(SASA): 0.789
• 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/Q	rs727504673	0.498	0.322	N	0.303	0.186	0.1749357433	gnomAD-2.1.1	2.01E-05	None	None	None	None	I	None	0	0	None	0	2.78583E-04	None	0	None	0	0	0
E/Q	rs727504673	0.498	0.322	N	0.303	0.186	0.1749357433	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/Q	rs727504673	0.498	0.322	N	0.303	0.186	0.1749357433	gnomAD-4.0.0	1.98316E-05	None	None	None	None	I	None	0	0	None	0	4.90502E-04	None	0	0	8.4766E-06	0	0
E/V	rs1705791323	None	0.991	N	0.565	0.504	0.459552425292	gnomAD-4.0.0	1.59145E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85869E-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	0.1853	likely_benign	0.1463	benign	-0.408	Destabilizing	0.939	D	0.567	neutral	N	0.444703401	None	None	I
E/C	0.8639	likely_pathogenic	0.7916	pathogenic	-0.242	Destabilizing	0.999	D	0.657	neutral	None	None	None	None	I
E/D	0.133	likely_benign	0.1066	benign	-0.429	Destabilizing	0.02	N	0.267	neutral	N	0.378723551	None	None	I
E/F	0.8118	likely_pathogenic	0.6947	pathogenic	-0.121	Destabilizing	0.999	D	0.635	neutral	None	None	None	None	I
E/G	0.1782	likely_benign	0.133	benign	-0.629	Destabilizing	0.939	D	0.516	neutral	N	0.458707274	None	None	I
E/H	0.6659	likely_pathogenic	0.5334	ambiguous	0.171	Stabilizing	0.998	D	0.502	neutral	None	None	None	None	I
E/I	0.4046	ambiguous	0.3053	benign	0.147	Stabilizing	0.993	D	0.645	neutral	None	None	None	None	I
E/K	0.2989	likely_benign	0.2111	benign	0.205	Stabilizing	0.885	D	0.557	neutral	N	0.480181412	None	None	I
E/L	0.4231	ambiguous	0.3199	benign	0.147	Stabilizing	0.986	D	0.614	neutral	None	None	None	None	I
E/M	0.4695	ambiguous	0.3808	ambiguous	0.139	Stabilizing	0.998	D	0.591	neutral	None	None	None	None	I
E/N	0.3227	likely_benign	0.234	benign	-0.239	Destabilizing	0.986	D	0.493	neutral	None	None	None	None	I
E/P	0.6415	likely_pathogenic	0.5262	ambiguous	-0.017	Destabilizing	0.993	D	0.551	neutral	None	None	None	None	I
E/Q	0.2214	likely_benign	0.1738	benign	-0.176	Destabilizing	0.322	N	0.303	neutral	N	0.513832625	None	None	I
E/R	0.4619	ambiguous	0.3496	ambiguous	0.505	Stabilizing	0.973	D	0.513	neutral	None	None	None	None	I
E/S	0.261	likely_benign	0.1945	benign	-0.39	Destabilizing	0.953	D	0.535	neutral	None	None	None	None	I
E/T	0.2886	likely_benign	0.2104	benign	-0.204	Destabilizing	0.986	D	0.483	neutral	None	None	None	None	I
E/V	0.2281	likely_benign	0.1743	benign	-0.017	Destabilizing	0.991	D	0.565	neutral	N	0.458864777	None	None	I
E/W	0.9331	likely_pathogenic	0.8751	pathogenic	0.077	Stabilizing	0.999	D	0.666	neutral	None	None	None	None	I
E/Y	0.716	likely_pathogenic	0.5909	pathogenic	0.13	Stabilizing	0.998	D	0.599	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.