TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28260	85003;85004;85005	chr2:178561354;178561353;178561352	chr2:179426081;179426080;179426079
N2AB	26619	80080;80081;80082	chr2:178561354;178561353;178561352	chr2:179426081;179426080;179426079
N2A	25692	77299;77300;77301	chr2:178561354;178561353;178561352	chr2:179426081;179426080;179426079
N2B	19195	57808;57809;57810	chr2:178561354;178561353;178561352	chr2:179426081;179426080;179426079
Novex-1	19320	58183;58184;58185	chr2:178561354;178561353;178561352	chr2:179426081;179426080;179426079
Novex-2	19387	58384;58385;58386	chr2:178561354;178561353;178561352	chr2:179426081;179426080;179426079
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: Fn3-94
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.3398
• 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	rs370547473	-0.905	0.071	N	0.163	0.122	0.199424873507	gnomAD-2.1.1	4.02E-05	None	None	None	None	N	None	0	2.31777E-04	None	0	0	None	0	None	0	8.9E-06	1.65782E-04
E/D	rs370547473	-0.905	0.071	N	0.163	0.122	0.199424873507	gnomAD-3.1.2	9.2E-05	None	None	None	None	N	None	2.41E-05	8.52124E-04	0	0	0	None	0	0	0	0	0
E/D	rs370547473	-0.905	0.071	N	0.163	0.122	0.199424873507	gnomAD-4.0.0	1.79707E-05	None	None	None	None	N	None	1.33469E-05	3.66801E-04	None	0	0	None	0	0	3.39036E-06	0	3.20215E-05

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	0.1721	likely_benign	0.1684	benign	-0.627	Destabilizing	0.961	D	0.51	neutral	N	0.477863245	None	None	N
E/C	0.7945	likely_pathogenic	0.7968	pathogenic	-0.363	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
E/D	0.2008	likely_benign	0.2138	benign	-0.78	Destabilizing	0.071	N	0.163	neutral	N	0.487168862	None	None	N
E/F	0.697	likely_pathogenic	0.6843	pathogenic	-0.201	Destabilizing	0.999	D	0.746	deleterious	None	None	None	None	N
E/G	0.3233	likely_benign	0.3417	ambiguous	-0.93	Destabilizing	0.98	D	0.587	neutral	N	0.497550889	None	None	N
E/H	0.4393	ambiguous	0.4291	ambiguous	-0.309	Destabilizing	0.999	D	0.552	neutral	None	None	None	None	N
E/I	0.2044	likely_benign	0.1911	benign	0.177	Stabilizing	0.999	D	0.743	deleterious	None	None	None	None	N
E/K	0.159	likely_benign	0.1481	benign	-0.345	Destabilizing	0.835	D	0.483	neutral	N	0.505490862	None	None	N
E/L	0.3374	likely_benign	0.329	benign	0.177	Stabilizing	0.991	D	0.663	neutral	None	None	None	None	N
E/M	0.3425	ambiguous	0.3315	benign	0.372	Stabilizing	1.0	D	0.71	prob.delet.	None	None	None	None	N
E/N	0.3276	likely_benign	0.3249	benign	-0.723	Destabilizing	0.97	D	0.478	neutral	None	None	None	None	N
E/P	0.956	likely_pathogenic	0.9588	pathogenic	-0.069	Destabilizing	0.999	D	0.635	neutral	None	None	None	None	N
E/Q	0.1333	likely_benign	0.1284	benign	-0.624	Destabilizing	0.961	D	0.493	neutral	N	0.520537672	None	None	N
E/R	0.2557	likely_benign	0.243	benign	-0.048	Destabilizing	0.092	N	0.189	neutral	None	None	None	None	N
E/S	0.2417	likely_benign	0.2428	benign	-0.952	Destabilizing	0.97	D	0.451	neutral	None	None	None	None	N
E/T	0.1943	likely_benign	0.1852	benign	-0.711	Destabilizing	0.985	D	0.553	neutral	None	None	None	None	N
E/V	0.1199	likely_benign	0.1177	benign	-0.069	Destabilizing	0.994	D	0.662	neutral	N	0.487638607	None	None	N
E/W	0.8928	likely_pathogenic	0.8933	pathogenic	0.01	Stabilizing	1.0	D	0.766	deleterious	None	None	None	None	N
E/Y	0.6146	likely_pathogenic	0.6084	pathogenic	0.031	Stabilizing	0.999	D	0.729	prob.delet.	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.