TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9124	27595;27596;27597	chr2:178712552;178712551;178712550	chr2:179577279;179577278;179577277
N2AB	8807	26644;26645;26646	chr2:178712552;178712551;178712550	chr2:179577279;179577278;179577277
N2A	7880	23863;23864;23865	chr2:178712552;178712551;178712550	chr2:179577279;179577278;179577277
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-77
• Domain position: 13
• Structural Position: 18
• Q(SASA): 0.7427
• 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/D	None	None	0.026	N	0.284	0.046	0.158396225186	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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	0.2327	likely_benign	0.2255	benign	-0.478	Destabilizing	0.896	D	0.569	neutral	D	0.525304066	None	None	I
E/C	0.9275	likely_pathogenic	0.9127	pathogenic	-0.274	Destabilizing	0.999	D	0.703	prob.neutral	None	None	None	None	I
E/D	0.2965	likely_benign	0.2676	benign	-0.43	Destabilizing	0.026	N	0.284	neutral	N	0.496368025	None	None	I
E/F	0.8464	likely_pathogenic	0.8294	pathogenic	-0.132	Destabilizing	0.996	D	0.64	neutral	None	None	None	None	I
E/G	0.2366	likely_benign	0.2415	benign	-0.696	Destabilizing	0.896	D	0.598	neutral	N	0.51305343	None	None	I
E/H	0.6534	likely_pathogenic	0.6322	pathogenic	0.244	Stabilizing	0.988	D	0.481	neutral	None	None	None	None	I
E/I	0.4383	ambiguous	0.4312	ambiguous	0.074	Stabilizing	0.988	D	0.643	neutral	None	None	None	None	I
E/K	0.1955	likely_benign	0.1994	benign	0.274	Stabilizing	0.811	D	0.53	neutral	N	0.487439111	None	None	I
E/L	0.4647	ambiguous	0.4579	ambiguous	0.074	Stabilizing	0.976	D	0.611	neutral	None	None	None	None	I
E/M	0.574	likely_pathogenic	0.5605	ambiguous	0.067	Stabilizing	0.999	D	0.64	neutral	None	None	None	None	I
E/N	0.4898	ambiguous	0.4603	ambiguous	-0.283	Destabilizing	0.261	N	0.313	neutral	None	None	None	None	I
E/P	0.5225	ambiguous	0.5055	ambiguous	-0.09	Destabilizing	0.988	D	0.543	neutral	None	None	None	None	I
E/Q	0.1497	likely_benign	0.1541	benign	-0.216	Destabilizing	0.437	N	0.301	neutral	N	0.507006306	None	None	I
E/R	0.3229	likely_benign	0.3279	benign	0.601	Stabilizing	0.976	D	0.479	neutral	None	None	None	None	I
E/S	0.3593	ambiguous	0.3398	benign	-0.411	Destabilizing	0.919	D	0.519	neutral	None	None	None	None	I
E/T	0.3608	ambiguous	0.3425	ambiguous	-0.22	Destabilizing	0.919	D	0.532	neutral	None	None	None	None	I
E/V	0.2714	likely_benign	0.2624	benign	-0.09	Destabilizing	0.984	D	0.591	neutral	D	0.526517574	None	None	I
E/W	0.9426	likely_pathogenic	0.9359	pathogenic	0.101	Stabilizing	0.999	D	0.709	prob.delet.	None	None	None	None	I
E/Y	0.7771	likely_pathogenic	0.7526	pathogenic	0.131	Stabilizing	0.996	D	0.623	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.