TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17285	52078;52079;52080	chr2:178609457;178609456;178609455	chr2:179474184;179474183;179474182
N2AB	15644	47155;47156;47157	chr2:178609457;178609456;178609455	chr2:179474184;179474183;179474182
N2A	14717	44374;44375;44376	chr2:178609457;178609456;178609455	chr2:179474184;179474183;179474182
N2B	8220	24883;24884;24885	chr2:178609457;178609456;178609455	chr2:179474184;179474183;179474182
Novex-1	8345	25258;25259;25260	chr2:178609457;178609456;178609455	chr2:179474184;179474183;179474182
Novex-2	8412	25459;25460;25461	chr2:178609457;178609456;178609455	chr2:179474184;179474183;179474182
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-112
• Domain position: 35
• Structural Position: 52
• Q(SASA): 0.3388
• 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/A	None	None	None	N	0.211	0.198	0.203808441222	gnomAD-4.0.0	1.36947E-06	None	None	None	None	N	None	2.99365E-05	0	None	0	0	None	0	1.73792E-04	0	0	0
E/G	None	None	0.024	N	0.387	0.192	0.151104730317	gnomAD-4.0.0	6.84734E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.16009E-05	0
E/K	rs1355045941	0.309	0.024	N	0.452	0.177	0.184867976434	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
E/K	rs1355045941	0.309	0.024	N	0.452	0.177	0.184867976434	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/K	rs1355045941	0.309	0.024	N	0.452	0.177	0.184867976434	gnomAD-4.0.0	2.56677E-06	None	None	None	None	N	None	0	1.69716E-05	None	0	0	None	0	0	2.39686E-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	0.1676	likely_benign	0.176	benign	-0.206	Destabilizing	None	N	0.211	neutral	N	0.501442118	None	None	N
E/C	0.7808	likely_pathogenic	0.7825	pathogenic	-0.121	Destabilizing	0.864	D	0.591	neutral	None	None	None	None	N
E/D	0.0712	likely_benign	0.0739	benign	-0.247	Destabilizing	None	N	0.134	neutral	N	0.394042507	None	None	N
E/F	0.7893	likely_pathogenic	0.8107	pathogenic	-0.093	Destabilizing	0.628	D	0.607	neutral	None	None	None	None	N
E/G	0.0865	likely_benign	0.0847	benign	-0.386	Destabilizing	0.024	N	0.387	neutral	N	0.387300175	None	None	N
E/H	0.3956	ambiguous	0.4076	ambiguous	0.323	Stabilizing	0.356	N	0.589	neutral	None	None	None	None	N
E/I	0.4745	ambiguous	0.4922	ambiguous	0.227	Stabilizing	0.356	N	0.645	neutral	None	None	None	None	N
E/K	0.1232	likely_benign	0.1223	benign	0.33	Stabilizing	0.024	N	0.452	neutral	N	0.470945853	None	None	N
E/L	0.5218	ambiguous	0.5381	ambiguous	0.227	Stabilizing	0.072	N	0.546	neutral	None	None	None	None	N
E/M	0.5133	ambiguous	0.5326	ambiguous	0.146	Stabilizing	0.628	D	0.591	neutral	None	None	None	None	N
E/N	0.1177	likely_benign	0.1248	benign	0.043	Stabilizing	None	N	0.163	neutral	None	None	None	None	N
E/P	0.6055	likely_pathogenic	0.5684	pathogenic	0.103	Stabilizing	0.136	N	0.625	neutral	None	None	None	None	N
E/Q	0.1351	likely_benign	0.1379	benign	0.088	Stabilizing	0.055	N	0.447	neutral	N	0.490841122	None	None	N
E/R	0.2278	likely_benign	0.2292	benign	0.602	Stabilizing	0.072	N	0.524	neutral	None	None	None	None	N
E/S	0.1404	likely_benign	0.1489	benign	-0.13	Destabilizing	0.016	N	0.339	neutral	None	None	None	None	N
E/T	0.1991	likely_benign	0.2123	benign	0.02	Stabilizing	0.031	N	0.493	neutral	None	None	None	None	N
E/V	0.3295	likely_benign	0.3398	benign	0.103	Stabilizing	0.055	N	0.527	neutral	N	0.455972057	None	None	N
E/W	0.8859	likely_pathogenic	0.8826	pathogenic	0.024	Stabilizing	0.864	D	0.616	neutral	None	None	None	None	N
E/Y	0.6081	likely_pathogenic	0.6146	pathogenic	0.144	Stabilizing	0.628	D	0.607	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.