TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27710	83353;83354;83355	chr2:178563004;178563003;178563002	chr2:179427731;179427730;179427729
N2AB	26069	78430;78431;78432	chr2:178563004;178563003;178563002	chr2:179427731;179427730;179427729
N2A	25142	75649;75650;75651	chr2:178563004;178563003;178563002	chr2:179427731;179427730;179427729
N2B	18645	56158;56159;56160	chr2:178563004;178563003;178563002	chr2:179427731;179427730;179427729
Novex-1	18770	56533;56534;56535	chr2:178563004;178563003;178563002	chr2:179427731;179427730;179427729
Novex-2	18837	56734;56735;56736	chr2:178563004;178563003;178563002	chr2:179427731;179427730;179427729
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: Ig-141
• Domain position: 35
• Structural Position: 49
• Q(SASA): 0.3821
• 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/K	rs1296454749	None	0.028	N	0.172	0.157	0.124217242631	gnomAD-4.0.0	4.78976E-06	None	None	None	None	N	None	0	0	None	0	2.52029E-05	None	0	0	5.39709E-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	0.1868	likely_benign	0.1857	benign	-0.828	Destabilizing	0.309	N	0.455	neutral	N	0.43944951	None	None	N
E/C	0.815	likely_pathogenic	0.8125	pathogenic	-0.412	Destabilizing	0.996	D	0.599	neutral	None	None	None	None	N
E/D	0.2278	likely_benign	0.2271	benign	-1.12	Destabilizing	0.472	N	0.443	neutral	N	0.474716877	None	None	N
E/F	0.8047	likely_pathogenic	0.7902	pathogenic	-0.284	Destabilizing	0.984	D	0.609	neutral	None	None	None	None	N
E/G	0.21	likely_benign	0.1905	benign	-1.2	Destabilizing	0.684	D	0.543	neutral	N	0.451013298	None	None	N
E/H	0.5038	ambiguous	0.483	ambiguous	-0.575	Destabilizing	0.953	D	0.533	neutral	None	None	None	None	N
E/I	0.4049	ambiguous	0.3736	ambiguous	0.184	Stabilizing	0.953	D	0.612	neutral	None	None	None	None	N
E/K	0.2351	likely_benign	0.2099	benign	-0.495	Destabilizing	0.028	N	0.172	neutral	N	0.410646756	None	None	N
E/L	0.4666	ambiguous	0.4371	ambiguous	0.184	Stabilizing	0.742	D	0.569	neutral	None	None	None	None	N
E/M	0.4574	ambiguous	0.4382	ambiguous	0.64	Stabilizing	0.996	D	0.585	neutral	None	None	None	None	N
E/N	0.3287	likely_benign	0.3074	benign	-1.012	Destabilizing	0.742	D	0.439	neutral	None	None	None	None	N
E/P	0.9849	likely_pathogenic	0.9827	pathogenic	-0.131	Destabilizing	0.953	D	0.575	neutral	None	None	None	None	N
E/Q	0.1257	likely_benign	0.1204	benign	-0.873	Destabilizing	0.684	D	0.429	neutral	N	0.452917453	None	None	N
E/R	0.3506	ambiguous	0.3227	benign	-0.251	Destabilizing	0.009	N	0.303	neutral	None	None	None	None	N
E/S	0.1992	likely_benign	0.1922	benign	-1.322	Destabilizing	0.045	N	0.161	neutral	None	None	None	None	N
E/T	0.195	likely_benign	0.1844	benign	-1.007	Destabilizing	0.59	D	0.511	neutral	None	None	None	None	N
E/V	0.2304	likely_benign	0.2169	benign	-0.131	Destabilizing	0.815	D	0.586	neutral	N	0.468558909	None	None	N
E/W	0.921	likely_pathogenic	0.9148	pathogenic	-0.028	Destabilizing	0.996	D	0.621	neutral	None	None	None	None	N
E/Y	0.7178	likely_pathogenic	0.704	pathogenic	-0.02	Destabilizing	0.984	D	0.605	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.