TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7303	22132;22133;22134	chr2:178723100;178723099;178723098	chr2:179587827;179587826;179587825
N2AB	6986	21181;21182;21183	chr2:178723100;178723099;178723098	chr2:179587827;179587826;179587825
N2A	6059	18400;18401;18402	chr2:178723100;178723099;178723098	chr2:179587827;179587826;179587825
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-57
• Domain position: 74
• Structural Position: 157
• Q(SASA): 0.2221
• 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	0.549	N	0.646	0.391	0.49179695788	gnomAD-4.0.0	3.18351E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71817E-06	0	0
E/K	rs774950387	-1.245	0.084	N	0.275	0.221	0.332133492242	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	2.67E-05	0
E/K	rs774950387	-1.245	0.084	N	0.275	0.221	0.332133492242	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	2.94E-05	0	0
E/K	rs774950387	-1.245	0.084	N	0.275	0.221	0.332133492242	gnomAD-4.0.0	1.54945E-05	None	None	None	None	N	None	2.6708E-05	0	None	0	0	None	0	0	1.52585E-05	0	8.00692E-05
E/Q	rs774950387	None	0.756	N	0.587	0.122	0.263140351381	gnomAD-4.0.0	6.84304E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99556E-07	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	0.1485	likely_benign	0.1586	benign	-1.035	Destabilizing	0.201	N	0.564	neutral	N	0.516396581	None	None	N
E/C	0.6814	likely_pathogenic	0.73	pathogenic	-0.665	Destabilizing	0.977	D	0.697	prob.neutral	None	None	None	None	N
E/D	0.205	likely_benign	0.2261	benign	-1.444	Destabilizing	0.549	D	0.553	neutral	N	0.493797086	None	None	N
E/F	0.4838	ambiguous	0.5167	ambiguous	-0.547	Destabilizing	0.85	D	0.709	prob.delet.	None	None	None	None	N
E/G	0.2206	likely_benign	0.2518	benign	-1.45	Destabilizing	0.549	D	0.646	neutral	N	0.502697856	None	None	N
E/H	0.278	likely_benign	0.2992	benign	-0.88	Destabilizing	0.012	N	0.376	neutral	None	None	None	None	N
E/I	0.1691	likely_benign	0.1744	benign	0.124	Stabilizing	0.217	N	0.688	prob.neutral	None	None	None	None	N
E/K	0.1244	likely_benign	0.1316	benign	-1.061	Destabilizing	0.084	N	0.275	neutral	N	0.50721695	None	None	N
E/L	0.2511	likely_benign	0.2641	benign	0.124	Stabilizing	0.447	N	0.648	neutral	None	None	None	None	N
E/M	0.2815	likely_benign	0.2943	benign	0.706	Stabilizing	0.85	D	0.661	neutral	None	None	None	None	N
E/N	0.2554	likely_benign	0.2871	benign	-1.457	Destabilizing	0.617	D	0.598	neutral	None	None	None	None	N
E/P	0.9598	likely_pathogenic	0.9657	pathogenic	-0.242	Destabilizing	0.972	D	0.646	neutral	None	None	None	None	N
E/Q	0.1036	likely_benign	0.1092	benign	-1.26	Destabilizing	0.756	D	0.587	neutral	N	0.494634442	None	None	N
E/R	0.19	likely_benign	0.1943	benign	-0.859	Destabilizing	0.005	N	0.376	neutral	None	None	None	None	N
E/S	0.1908	likely_benign	0.2033	benign	-1.943	Destabilizing	0.617	D	0.572	neutral	None	None	None	None	N
E/T	0.1698	likely_benign	0.1761	benign	-1.582	Destabilizing	0.617	D	0.609	neutral	None	None	None	None	N
E/V	0.1162	likely_benign	0.117	benign	-0.242	Destabilizing	0.004	N	0.581	neutral	N	0.449363512	None	None	N
E/W	0.7517	likely_pathogenic	0.7687	pathogenic	-0.416	Destabilizing	0.992	D	0.708	prob.delet.	None	None	None	None	N
E/Y	0.422	ambiguous	0.4448	ambiguous	-0.311	Destabilizing	0.85	D	0.674	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.