TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3958	12097;12098;12099	chr2:178741361;178741360;178741359	chr2:179606088;179606087;179606086
N2AB	3641	11146;11147;11148	chr2:178741361;178741360;178741359	chr2:179606088;179606087;179606086
N2A	None	None	chr2:None	chr2:None
N2B	3595	11008;11009;11010	chr2:178741361;178741360;178741359	chr2:179606088;179606087;179606086
Novex-1	3720	11383;11384;11385	chr2:178741361;178741360;178741359	chr2:179606088;179606087;179606086
Novex-2	3787	11584;11585;11586	chr2:178741361;178741360;178741359	chr2:179606088;179606087;179606086
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-28
• Domain position: 21
• Structural Position: 31
• Q(SASA): 0.4217
• 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	None	None	0.001	N	0.263	0.249	None	gnomAD-4.0.0	6.84175E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99437E-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	0.2112	likely_benign	0.2171	benign	-0.736	Destabilizing	0.081	N	0.427	neutral	D	0.552556776	None	None	I
E/C	0.8444	likely_pathogenic	0.8539	pathogenic	-0.32	Destabilizing	0.958	D	0.575	neutral	None	None	None	None	I
E/D	0.1486	likely_benign	0.1797	benign	-0.741	Destabilizing	0.001	N	0.231	neutral	N	0.514848004	None	None	I
E/F	0.8137	likely_pathogenic	0.8283	pathogenic	-0.015	Destabilizing	0.497	N	0.57	neutral	None	None	None	None	I
E/G	0.2181	likely_benign	0.2247	benign	-1.091	Destabilizing	0.175	N	0.526	neutral	D	0.667038756	None	None	I
E/H	0.4393	ambiguous	0.4554	ambiguous	-0.123	Destabilizing	0.002	N	0.356	neutral	None	None	None	None	I
E/I	0.5072	ambiguous	0.5261	ambiguous	0.228	Stabilizing	0.331	N	0.609	neutral	None	None	None	None	I
E/K	0.1623	likely_benign	0.1689	benign	-0.047	Destabilizing	0.001	N	0.263	neutral	N	0.51291992	None	None	I
E/L	0.5435	ambiguous	0.5609	ambiguous	0.228	Stabilizing	0.001	N	0.485	neutral	None	None	None	None	I
E/M	0.6016	likely_pathogenic	0.6211	pathogenic	0.513	Stabilizing	0.497	N	0.571	neutral	None	None	None	None	I
E/N	0.2723	likely_benign	0.3154	benign	-0.722	Destabilizing	0.001	N	0.385	neutral	None	None	None	None	I
E/P	0.6875	likely_pathogenic	0.714	pathogenic	-0.072	Destabilizing	0.667	D	0.572	neutral	None	None	None	None	I
E/Q	0.1489	likely_benign	0.1465	benign	-0.579	Destabilizing	0.008	N	0.379	neutral	N	0.5147779	None	None	I
E/R	0.2577	likely_benign	0.2655	benign	0.22	Stabilizing	0.124	N	0.391	neutral	None	None	None	None	I
E/S	0.2172	likely_benign	0.2328	benign	-0.981	Destabilizing	0.055	N	0.397	neutral	None	None	None	None	I
E/T	0.2551	likely_benign	0.2675	benign	-0.666	Destabilizing	0.22	N	0.469	neutral	None	None	None	None	I
E/V	0.3259	likely_benign	0.3428	ambiguous	-0.072	Destabilizing	0.096	N	0.533	neutral	D	0.547880284	None	None	I
E/W	0.9032	likely_pathogenic	0.9113	pathogenic	0.338	Stabilizing	0.958	D	0.592	neutral	None	None	None	None	I
E/Y	0.6503	likely_pathogenic	0.6714	pathogenic	0.294	Stabilizing	0.497	N	0.593	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.