TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31162	93709;93710;93711	chr2:178548142;178548141;178548140	chr2:179412869;179412868;179412867
N2AB	29521	88786;88787;88788	chr2:178548142;178548141;178548140	chr2:179412869;179412868;179412867
N2A	28594	86005;86006;86007	chr2:178548142;178548141;178548140	chr2:179412869;179412868;179412867
N2B	22097	66514;66515;66516	chr2:178548142;178548141;178548140	chr2:179412869;179412868;179412867
Novex-1	22222	66889;66890;66891	chr2:178548142;178548141;178548140	chr2:179412869;179412868;179412867
Novex-2	22289	67090;67091;67092	chr2:178548142;178548141;178548140	chr2:179412869;179412868;179412867
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: Fn3-115
• Domain position: 50
• Structural Position: 67
• Q(SASA): 0.6217
• 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	rs1553529185	None	0.001	N	0.217	0.167	0.21279746466	gnomAD-4.0.0	3.18211E-06	None	None	None	None	N	None	0	0	None	4.76599E-05	0	None	0	0	0	0	3.02389E-05
E/K	rs762566802	None	0.491	N	0.299	0.222	0.206339911435	gnomAD-4.0.0	1.20032E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-05	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	0.1079	likely_benign	0.1247	benign	-0.695	Destabilizing	0.001	N	0.217	neutral	N	0.446930922	None	None	N
E/C	0.7245	likely_pathogenic	0.7732	pathogenic	-0.346	Destabilizing	0.972	D	0.455	neutral	None	None	None	None	N
E/D	0.156	likely_benign	0.1892	benign	-0.742	Destabilizing	0.662	D	0.318	neutral	N	0.455993122	None	None	N
E/F	0.6588	likely_pathogenic	0.7335	pathogenic	-0.359	Destabilizing	0.004	N	0.351	neutral	None	None	None	None	N
E/G	0.1966	likely_benign	0.2118	benign	-0.971	Destabilizing	0.001	N	0.254	neutral	N	0.499879972	None	None	N
E/H	0.4341	ambiguous	0.463	ambiguous	-0.33	Destabilizing	0.965	D	0.432	neutral	None	None	None	None	N
E/I	0.2127	likely_benign	0.2766	benign	0.031	Stabilizing	0.209	N	0.451	neutral	None	None	None	None	N
E/K	0.1436	likely_benign	0.1538	benign	-0.299	Destabilizing	0.491	N	0.299	neutral	N	0.387498616	None	None	N
E/L	0.2505	likely_benign	0.3127	benign	0.031	Stabilizing	0.002	N	0.34	neutral	None	None	None	None	N
E/M	0.3022	likely_benign	0.3585	ambiguous	0.249	Stabilizing	0.818	D	0.469	neutral	None	None	None	None	N
E/N	0.2506	likely_benign	0.3157	benign	-0.643	Destabilizing	0.561	D	0.384	neutral	None	None	None	None	N
E/P	0.2563	likely_benign	0.3062	benign	-0.19	Destabilizing	0.004	N	0.254	neutral	None	None	None	None	N
E/Q	0.1363	likely_benign	0.1395	benign	-0.57	Destabilizing	0.662	D	0.387	neutral	N	0.452240741	None	None	N
E/R	0.2404	likely_benign	0.2493	benign	0.033	Stabilizing	0.722	D	0.404	neutral	None	None	None	None	N
E/S	0.1748	likely_benign	0.2139	benign	-0.867	Destabilizing	0.209	N	0.292	neutral	None	None	None	None	N
E/T	0.1651	likely_benign	0.2039	benign	-0.649	Destabilizing	0.345	N	0.423	neutral	None	None	None	None	N
E/V	0.1201	likely_benign	0.1538	benign	-0.19	Destabilizing	0.005	N	0.237	neutral	N	0.44065831	None	None	N
E/W	0.8777	likely_pathogenic	0.8872	pathogenic	-0.146	Destabilizing	0.991	D	0.469	neutral	None	None	None	None	N
E/Y	0.5995	likely_pathogenic	0.6557	pathogenic	-0.124	Destabilizing	0.692	D	0.534	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.