TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22018	66277;66278;66279	chr2:178582404;178582403;178582402	chr2:179447131;179447130;179447129
N2AB	20377	61354;61355;61356	chr2:178582404;178582403;178582402	chr2:179447131;179447130;179447129
N2A	19450	58573;58574;58575	chr2:178582404;178582403;178582402	chr2:179447131;179447130;179447129
N2B	12953	39082;39083;39084	chr2:178582404;178582403;178582402	chr2:179447131;179447130;179447129
Novex-1	13078	39457;39458;39459	chr2:178582404;178582403;178582402	chr2:179447131;179447130;179447129
Novex-2	13145	39658;39659;39660	chr2:178582404;178582403;178582402	chr2:179447131;179447130;179447129
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: Fn3-47
• Domain position: 63
• Structural Position: 94
• Q(SASA): 0.5321
• 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	rs727503579	-0.374	0.014	N	0.29	0.031	0.245660935333	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	2.67E-05	0
E/D	rs727503579	-0.374	0.014	N	0.29	0.031	0.245660935333	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/D	rs727503579	-0.374	0.014	N	0.29	0.031	0.245660935333	gnomAD-4.0.0	2.48027E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.30692E-05	0	1.60251E-05
E/G	None	None	0.822	N	0.672	0.322	0.342631996419	gnomAD-4.0.0	1.20038E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31257E-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	0.3869	ambiguous	0.3624	ambiguous	-0.69	Destabilizing	0.698	D	0.612	neutral	N	0.51821223	None	None	N
E/C	0.9555	likely_pathogenic	0.9437	pathogenic	-0.323	Destabilizing	0.998	D	0.763	deleterious	None	None	None	None	N
E/D	0.1846	likely_benign	0.1714	benign	-0.692	Destabilizing	0.014	N	0.29	neutral	N	0.466321972	None	None	N
E/F	0.9367	likely_pathogenic	0.9318	pathogenic	-0.276	Destabilizing	0.978	D	0.769	deleterious	None	None	None	None	N
E/G	0.3206	likely_benign	0.2922	benign	-0.971	Destabilizing	0.822	D	0.672	neutral	N	0.476269607	None	None	N
E/H	0.7919	likely_pathogenic	0.7642	pathogenic	-0.252	Destabilizing	0.998	D	0.568	neutral	None	None	None	None	N
E/I	0.7368	likely_pathogenic	0.7344	pathogenic	0.049	Stabilizing	0.915	D	0.681	prob.neutral	None	None	None	None	N
E/K	0.4892	ambiguous	0.4623	ambiguous	-0.163	Destabilizing	0.822	D	0.512	neutral	N	0.440135448	None	None	N
E/L	0.7092	likely_pathogenic	0.6996	pathogenic	0.049	Stabilizing	0.754	D	0.659	neutral	None	None	None	None	N
E/M	0.7706	likely_pathogenic	0.7591	pathogenic	0.268	Stabilizing	0.994	D	0.755	deleterious	None	None	None	None	N
E/N	0.4939	ambiguous	0.4601	ambiguous	-0.612	Destabilizing	0.956	D	0.549	neutral	None	None	None	None	N
E/P	0.6435	likely_pathogenic	0.5745	pathogenic	-0.177	Destabilizing	0.978	D	0.714	prob.delet.	None	None	None	None	N
E/Q	0.291	likely_benign	0.2604	benign	-0.531	Destabilizing	0.97	D	0.56	neutral	N	0.463647026	None	None	N
E/R	0.6385	likely_pathogenic	0.6064	pathogenic	0.145	Stabilizing	0.956	D	0.587	neutral	None	None	None	None	N
E/S	0.3834	ambiguous	0.359	ambiguous	-0.816	Destabilizing	0.754	D	0.496	neutral	None	None	None	None	N
E/T	0.4101	ambiguous	0.3942	ambiguous	-0.586	Destabilizing	0.019	N	0.355	neutral	None	None	None	None	N
E/V	0.5189	ambiguous	0.5139	ambiguous	-0.177	Destabilizing	0.125	N	0.382	neutral	N	0.474845455	None	None	N
E/W	0.9694	likely_pathogenic	0.9666	pathogenic	-0.024	Destabilizing	0.998	D	0.743	deleterious	None	None	None	None	N
E/Y	0.8791	likely_pathogenic	0.8678	pathogenic	-0.023	Destabilizing	0.993	D	0.769	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.