TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9233	27922;27923;27924	chr2:178712133;178712132;178712131	chr2:179576860;179576859;179576858
N2AB	8916	26971;26972;26973	chr2:178712133;178712132;178712131	chr2:179576860;179576859;179576858
N2A	7989	24190;24191;24192	chr2:178712133;178712132;178712131	chr2:179576860;179576859;179576858
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: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-78
• Domain position: 29
• Structural Position: 43
• Q(SASA): 0.869
• 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	0.939	N	0.607	0.382	0.515995215087	gnomAD-4.0.0	4.77374E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.71651E-06	0	3.02371E-05

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	0.2158	likely_benign	0.2346	benign	-0.091	Destabilizing	0.939	D	0.607	neutral	N	0.519148884	None	None	I
E/C	0.9474	likely_pathogenic	0.9578	pathogenic	-0.285	Destabilizing	0.999	D	0.716	prob.delet.	None	None	None	None	I
E/D	0.1489	likely_benign	0.1886	benign	-0.345	Destabilizing	0.046	N	0.324	neutral	D	0.531750035	None	None	I
E/F	0.8738	likely_pathogenic	0.8882	pathogenic	-0.069	Destabilizing	0.999	D	0.664	neutral	None	None	None	None	I
E/G	0.2771	likely_benign	0.3592	ambiguous	-0.219	Destabilizing	0.939	D	0.579	neutral	N	0.501509768	None	None	I
E/H	0.6285	likely_pathogenic	0.6582	pathogenic	0.563	Stabilizing	0.999	D	0.549	neutral	None	None	None	None	I
E/I	0.5304	ambiguous	0.5757	pathogenic	0.193	Stabilizing	0.993	D	0.669	neutral	None	None	None	None	I
E/K	0.2147	likely_benign	0.2405	benign	0.345	Stabilizing	0.939	D	0.583	neutral	N	0.501312485	None	None	I
E/L	0.5785	likely_pathogenic	0.6193	pathogenic	0.193	Stabilizing	0.993	D	0.669	neutral	None	None	None	None	I
E/M	0.6421	likely_pathogenic	0.686	pathogenic	-0.053	Destabilizing	0.999	D	0.661	neutral	None	None	None	None	I
E/N	0.352	ambiguous	0.4056	ambiguous	0.041	Stabilizing	0.973	D	0.555	neutral	None	None	None	None	I
E/P	0.5837	likely_pathogenic	0.5511	ambiguous	0.116	Stabilizing	0.06	N	0.477	neutral	None	None	None	None	I
E/Q	0.1915	likely_benign	0.2193	benign	0.061	Stabilizing	0.991	D	0.522	neutral	D	0.524842706	None	None	I
E/R	0.3574	ambiguous	0.3835	ambiguous	0.634	Stabilizing	0.993	D	0.573	neutral	None	None	None	None	I
E/S	0.2852	likely_benign	0.3084	benign	-0.093	Destabilizing	0.953	D	0.583	neutral	None	None	None	None	I
E/T	0.38	ambiguous	0.4058	ambiguous	0.021	Stabilizing	0.986	D	0.538	neutral	None	None	None	None	I
E/V	0.3144	likely_benign	0.3489	ambiguous	0.116	Stabilizing	0.991	D	0.606	neutral	D	0.528192442	None	None	I
E/W	0.9578	likely_pathogenic	0.9692	pathogenic	0.003	Stabilizing	0.999	D	0.715	prob.delet.	None	None	None	None	I
E/Y	0.7737	likely_pathogenic	0.8035	pathogenic	0.158	Stabilizing	0.998	D	0.647	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.