TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9617	29074;29075;29076	chr2:178707718;178707717;178707716	chr2:179572445;179572444;179572443
N2AB	9300	28123;28124;28125	chr2:178707718;178707717;178707716	chr2:179572445;179572444;179572443
N2A	8373	25342;25343;25344	chr2:178707718;178707717;178707716	chr2:179572445;179572444;179572443
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-82
• Domain position: 28
• Structural Position: 42
• Q(SASA): 0.7598
• 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/K	rs144025230	0.805	0.454	None	0.393	0.209	None	gnomAD-2.1.1	4.28E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	9.35E-05	0
E/K	rs144025230	0.805	0.454	None	0.393	0.209	None	gnomAD-3.1.2	5.91E-05	None	None	None	None	I	None	0	0	0	0	1.9253E-04	None	0	0	1.17564E-04	0	0
E/K	rs144025230	0.805	0.454	None	0.393	0.209	None	1000 genomes	1.99681E-04	None	None	None	None	I	None	0	0	None	None	0	1E-03	None	None	None	0	None
E/K	rs144025230	0.805	0.454	None	0.393	0.209	None	gnomAD-4.0.0	3.22185E-05	None	None	None	None	I	None	0	0	None	0	4.45633E-05	None	0	0	4.06828E-05	0	3.20061E-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	0.153	likely_benign	0.1272	benign	-0.199	Destabilizing	0.022	N	0.116	neutral	None	None	None	None	I
E/C	0.9286	likely_pathogenic	0.8883	pathogenic	-0.246	Destabilizing	0.998	D	0.407	neutral	None	None	None	None	I
E/D	0.1545	likely_benign	0.1465	benign	-0.366	Destabilizing	0.625	D	0.411	neutral	None	None	None	None	I
E/F	0.8293	likely_pathogenic	0.736	pathogenic	-0.07	Destabilizing	0.991	D	0.439	neutral	None	None	None	None	I
E/G	0.2102	likely_benign	0.158	benign	-0.359	Destabilizing	0.801	D	0.396	neutral	None	None	None	None	I
E/H	0.5687	likely_pathogenic	0.4662	ambiguous	0.49	Stabilizing	0.974	D	0.394	neutral	None	None	None	None	I
E/I	0.4793	ambiguous	0.3761	ambiguous	0.176	Stabilizing	0.974	D	0.482	neutral	None	None	None	None	I
E/K	0.1753	likely_benign	0.1295	benign	0.375	Stabilizing	0.454	N	0.393	neutral	None	None	None	None	I
E/L	0.4527	ambiguous	0.3505	ambiguous	0.176	Stabilizing	0.842	D	0.513	neutral	None	None	None	None	I
E/M	0.5508	ambiguous	0.434	ambiguous	0.01	Stabilizing	0.974	D	0.416	neutral	None	None	None	None	I
E/N	0.3049	likely_benign	0.269	benign	-0.039	Destabilizing	0.842	D	0.44	neutral	None	None	None	None	I
E/P	0.315	likely_benign	0.3097	benign	0.07	Stabilizing	0.007	N	0.121	neutral	None	None	None	None	I
E/Q	0.1377	likely_benign	0.1118	benign	0.004	Stabilizing	0.051	N	0.136	neutral	None	None	None	None	I
E/R	0.327	likely_benign	0.2432	benign	0.677	Stabilizing	0.728	D	0.445	neutral	None	None	None	None	I
E/S	0.187	likely_benign	0.1662	benign	-0.157	Destabilizing	0.525	D	0.381	neutral	None	None	None	None	I
E/T	0.2749	likely_benign	0.216	benign	-0.015	Destabilizing	0.842	D	0.463	neutral	None	None	None	None	I
E/V	0.2762	likely_benign	0.2097	benign	0.07	Stabilizing	0.801	D	0.485	neutral	None	None	None	None	I
E/W	0.9535	likely_pathogenic	0.9168	pathogenic	0.056	Stabilizing	0.998	D	0.475	neutral	None	None	None	None	I
E/Y	0.7211	likely_pathogenic	0.6132	pathogenic	0.172	Stabilizing	0.991	D	0.438	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.