TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24781	74566;74567;74568	chr2:178571791;178571790;178571789	chr2:179436518;179436517;179436516
N2AB	23140	69643;69644;69645	chr2:178571791;178571790;178571789	chr2:179436518;179436517;179436516
N2A	22213	66862;66863;66864	chr2:178571791;178571790;178571789	chr2:179436518;179436517;179436516
N2B	15716	47371;47372;47373	chr2:178571791;178571790;178571789	chr2:179436518;179436517;179436516
Novex-1	15841	47746;47747;47748	chr2:178571791;178571790;178571789	chr2:179436518;179436517;179436516
Novex-2	15908	47947;47948;47949	chr2:178571791;178571790;178571789	chr2:179436518;179436517;179436516
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-133
• Domain position: 66
• Structural Position: 148
• Q(SASA): 0.711
• 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/A	None	None	0.309	N	0.419	0.264	0.258283824007	gnomAD-4.0.0	1.59184E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85941E-06	0	0
E/D	None	None	0.001	N	0.176	0.071	0.104622674875	gnomAD-4.0.0	1.36864E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79917E-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	0.1961	likely_benign	0.1934	benign	-0.313	Destabilizing	0.309	N	0.419	neutral	N	0.502098266	None	None	I
E/C	0.8621	likely_pathogenic	0.8562	pathogenic	0.045	Stabilizing	0.996	D	0.442	neutral	None	None	None	None	I
E/D	0.0798	likely_benign	0.0759	benign	-0.262	Destabilizing	0.001	N	0.176	neutral	N	0.438913579	None	None	I
E/F	0.8231	likely_pathogenic	0.8196	pathogenic	-0.337	Destabilizing	0.953	D	0.423	neutral	None	None	None	None	I
E/G	0.1861	likely_benign	0.1805	benign	-0.481	Destabilizing	0.521	D	0.431	neutral	N	0.512680619	None	None	I
E/H	0.5824	likely_pathogenic	0.5761	pathogenic	-0.044	Destabilizing	0.984	D	0.373	neutral	None	None	None	None	I
E/I	0.5171	ambiguous	0.5133	ambiguous	0.084	Stabilizing	0.953	D	0.434	neutral	None	None	None	None	I
E/K	0.2638	likely_benign	0.2537	benign	0.338	Stabilizing	0.684	D	0.446	neutral	N	0.511603184	None	None	I
E/L	0.5372	ambiguous	0.5386	ambiguous	0.084	Stabilizing	0.91	D	0.405	neutral	None	None	None	None	I
E/M	0.5747	likely_pathogenic	0.5758	pathogenic	0.187	Stabilizing	0.996	D	0.413	neutral	None	None	None	None	I
E/N	0.233	likely_benign	0.2227	benign	0.147	Stabilizing	0.742	D	0.395	neutral	None	None	None	None	I
E/P	0.7162	likely_pathogenic	0.7123	pathogenic	-0.028	Destabilizing	0.953	D	0.381	neutral	None	None	None	None	I
E/Q	0.2358	likely_benign	0.2329	benign	0.16	Stabilizing	0.684	D	0.427	neutral	N	0.515182207	None	None	I
E/R	0.4173	ambiguous	0.4056	ambiguous	0.517	Stabilizing	0.91	D	0.385	neutral	None	None	None	None	I
E/S	0.2084	likely_benign	0.2025	benign	-0.032	Destabilizing	0.037	N	0.289	neutral	None	None	None	None	I
E/T	0.2722	likely_benign	0.2641	benign	0.101	Stabilizing	0.59	D	0.396	neutral	None	None	None	None	I
E/V	0.3256	likely_benign	0.322	benign	-0.028	Destabilizing	0.884	D	0.403	neutral	N	0.477789749	None	None	I
E/W	0.9012	likely_pathogenic	0.8989	pathogenic	-0.243	Destabilizing	0.996	D	0.56	neutral	None	None	None	None	I
E/Y	0.6846	likely_pathogenic	0.6752	pathogenic	-0.108	Destabilizing	0.984	D	0.418	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.