TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24230	72913;72914;72915	chr2:178573444;178573443;178573442	chr2:179438171;179438170;179438169
N2AB	22589	67990;67991;67992	chr2:178573444;178573443;178573442	chr2:179438171;179438170;179438169
N2A	21662	65209;65210;65211	chr2:178573444;178573443;178573442	chr2:179438171;179438170;179438169
N2B	15165	45718;45719;45720	chr2:178573444;178573443;178573442	chr2:179438171;179438170;179438169
Novex-1	15290	46093;46094;46095	chr2:178573444;178573443;178573442	chr2:179438171;179438170;179438169
Novex-2	15357	46294;46295;46296	chr2:178573444;178573443;178573442	chr2:179438171;179438170;179438169
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: Fn3-64
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.5794
• 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	rs771181715	None	0.805	N	0.614	0.324	0.43965937752	gnomAD-2.1.1	5.72E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.17E-05	0
E/A	rs771181715	None	0.805	N	0.614	0.324	0.43965937752	gnomAD-4.0.0	1.87812E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.26631E-06	0	0
E/K	None	None	0.944	N	0.557	0.364	0.39162414616	gnomAD-4.0.0	1.87826E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.26522E-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	0.2059	likely_benign	0.2445	benign	-0.72	Destabilizing	0.805	D	0.614	neutral	N	0.486257036	None	None	N
E/C	0.8304	likely_pathogenic	0.877	pathogenic	-0.343	Destabilizing	0.999	D	0.797	deleterious	None	None	None	None	N
E/D	0.1566	likely_benign	0.1842	benign	-0.809	Destabilizing	0.981	D	0.501	neutral	N	0.494410564	None	None	N
E/F	0.7687	likely_pathogenic	0.8188	pathogenic	-0.295	Destabilizing	0.975	D	0.792	deleterious	None	None	None	None	N
E/G	0.3731	ambiguous	0.3988	ambiguous	-1.028	Destabilizing	0.983	D	0.69	prob.neutral	N	0.506438432	None	None	N
E/H	0.5049	ambiguous	0.5735	pathogenic	-0.422	Destabilizing	0.999	D	0.661	neutral	None	None	None	None	N
E/I	0.3028	likely_benign	0.359	ambiguous	0.104	Stabilizing	0.95	D	0.717	prob.delet.	None	None	None	None	N
E/K	0.2131	likely_benign	0.2355	benign	-0.405	Destabilizing	0.944	D	0.557	neutral	N	0.481517924	None	None	N
E/L	0.4309	ambiguous	0.5098	ambiguous	0.104	Stabilizing	0.845	D	0.689	prob.neutral	None	None	None	None	N
E/M	0.4393	ambiguous	0.5064	ambiguous	0.399	Stabilizing	0.997	D	0.775	deleterious	None	None	None	None	N
E/N	0.3145	likely_benign	0.3821	ambiguous	-0.769	Destabilizing	0.996	D	0.666	neutral	None	None	None	None	N
E/P	0.9501	likely_pathogenic	0.9667	pathogenic	-0.15	Destabilizing	0.996	D	0.783	deleterious	None	None	None	None	N
E/Q	0.1683	likely_benign	0.191	benign	-0.661	Destabilizing	0.994	D	0.643	neutral	N	0.518113442	None	None	N
E/R	0.3453	ambiguous	0.3816	ambiguous	-0.107	Destabilizing	0.987	D	0.674	neutral	None	None	None	None	N
E/S	0.246	likely_benign	0.2904	benign	-1.014	Destabilizing	0.957	D	0.598	neutral	None	None	None	None	N
E/T	0.2201	likely_benign	0.2637	benign	-0.766	Destabilizing	0.975	D	0.763	deleterious	None	None	None	None	N
E/V	0.1779	likely_benign	0.2143	benign	-0.15	Destabilizing	0.056	N	0.465	neutral	N	0.46707637	None	None	N
E/W	0.9212	likely_pathogenic	0.9393	pathogenic	-0.071	Destabilizing	0.999	D	0.795	deleterious	None	None	None	None	N
E/Y	0.6658	likely_pathogenic	0.7264	pathogenic	-0.061	Destabilizing	0.987	D	0.788	deleterious	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.