TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26531	79816;79817;79818	chr2:178566541;178566540;178566539	chr2:179431268;179431267;179431266
N2AB	24890	74893;74894;74895	chr2:178566541;178566540;178566539	chr2:179431268;179431267;179431266
N2A	23963	72112;72113;72114	chr2:178566541;178566540;178566539	chr2:179431268;179431267;179431266
N2B	17466	52621;52622;52623	chr2:178566541;178566540;178566539	chr2:179431268;179431267;179431266
Novex-1	17591	52996;52997;52998	chr2:178566541;178566540;178566539	chr2:179431268;179431267;179431266
Novex-2	17658	53197;53198;53199	chr2:178566541;178566540;178566539	chr2:179431268;179431267;179431266
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: Fn3-81
• Domain position: 45
• Structural Position: 60
• Q(SASA): 0.4503
• 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/D	None	None	0.067	N	0.253	0.073	0.256793551483	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31251E-06	0	0
E/K	rs772211147	0.33	0.958	N	0.437	0.354	0.356072328145	gnomAD-2.1.1	8.06E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	8.91E-06	0
E/K	rs772211147	0.33	0.958	N	0.437	0.354	0.356072328145	gnomAD-4.0.0	1.9163E-05	None	None	None	None	N	None	0	2.23624E-05	None	0	0	None	0	0	2.33875E-05	0	1.65695E-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	0.1223	likely_benign	0.1312	benign	-0.414	Destabilizing	0.958	D	0.493	neutral	N	0.484542373	None	None	N
E/C	0.6903	likely_pathogenic	0.7434	pathogenic	0.026	Stabilizing	1.0	D	0.742	deleterious	None	None	None	None	N
E/D	0.107	likely_benign	0.1175	benign	-0.484	Destabilizing	0.067	N	0.253	neutral	N	0.484406301	None	None	N
E/F	0.6778	likely_pathogenic	0.7332	pathogenic	-0.495	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
E/G	0.1182	likely_benign	0.1301	benign	-0.625	Destabilizing	0.988	D	0.538	neutral	N	0.498527604	None	None	N
E/H	0.3775	ambiguous	0.4516	ambiguous	-0.525	Destabilizing	1.0	D	0.609	neutral	None	None	None	None	N
E/I	0.2961	likely_benign	0.3355	benign	0.108	Stabilizing	0.995	D	0.715	prob.delet.	None	None	None	None	N
E/K	0.1038	likely_benign	0.1222	benign	-0.023	Destabilizing	0.958	D	0.437	neutral	N	0.503973496	None	None	N
E/L	0.2903	likely_benign	0.3329	benign	0.108	Stabilizing	0.995	D	0.687	prob.neutral	None	None	None	None	N
E/M	0.3218	likely_benign	0.3591	ambiguous	0.376	Stabilizing	1.0	D	0.659	neutral	None	None	None	None	N
E/N	0.1881	likely_benign	0.22	benign	-0.112	Destabilizing	0.982	D	0.571	neutral	None	None	None	None	N
E/P	0.7282	likely_pathogenic	0.7889	pathogenic	-0.045	Destabilizing	0.995	D	0.586	neutral	None	None	None	None	N
E/Q	0.1239	likely_benign	0.1399	benign	-0.093	Destabilizing	0.994	D	0.521	neutral	N	0.473712642	None	None	N
E/R	0.1971	likely_benign	0.2395	benign	0.114	Stabilizing	0.995	D	0.589	neutral	None	None	None	None	N
E/S	0.146	likely_benign	0.1625	benign	-0.324	Destabilizing	0.968	D	0.452	neutral	None	None	None	None	N
E/T	0.137	likely_benign	0.1521	benign	-0.171	Destabilizing	0.991	D	0.571	neutral	None	None	None	None	N
E/V	0.1717	likely_benign	0.1899	benign	-0.045	Destabilizing	0.994	D	0.62	neutral	N	0.513691844	None	None	N
E/W	0.8422	likely_pathogenic	0.8862	pathogenic	-0.437	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
E/Y	0.5313	ambiguous	0.6089	pathogenic	-0.294	Destabilizing	1.0	D	0.659	neutral	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.