TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21729	65410;65411;65412	chr2:178584366;178584365;178584364	chr2:179449093;179449092;179449091
N2AB	20088	60487;60488;60489	chr2:178584366;178584365;178584364	chr2:179449093;179449092;179449091
N2A	19161	57706;57707;57708	chr2:178584366;178584365;178584364	chr2:179449093;179449092;179449091
N2B	12664	38215;38216;38217	chr2:178584366;178584365;178584364	chr2:179449093;179449092;179449091
Novex-1	12789	38590;38591;38592	chr2:178584366;178584365;178584364	chr2:179449093;179449092;179449091
Novex-2	12856	38791;38792;38793	chr2:178584366;178584365;178584364	chr2:179449093;179449092;179449091
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: Fn3-45
• Domain position: 71
• Structural Position: 103
• Q(SASA): 0.2339
• 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/G	rs1317452229	None	1.0	N	0.733	0.563	0.465549362696	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/G	rs1317452229	None	1.0	N	0.733	0.563	0.465549362696	gnomAD-4.0.0	6.57531E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47102E-05	0	0
E/K	rs375439506	-0.607	0.999	N	0.611	0.424	0.326074293725	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	6.47E-05	0	None	0	0	None	0	None	0	0	0
E/K	rs375439506	-0.607	0.999	N	0.611	0.424	0.326074293725	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
E/K	rs375439506	-0.607	0.999	N	0.611	0.424	0.326074293725	gnomAD-4.0.0	4.33928E-06	None	None	None	None	N	None	2.67094E-05	0	None	0	0	None	0	1.64582E-04	1.69567E-06	1.09835E-05	1.60179E-05
E/Q	rs375439506	None	1.0	N	0.631	0.392	None	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
E/Q	rs375439506	None	1.0	N	0.631	0.392	None	gnomAD-4.0.0	2.47959E-06	None	None	None	None	N	None	2.67094E-05	0	None	0	0	None	0	0	0	2.19669E-05	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	0.5226	ambiguous	0.4614	ambiguous	-0.779	Destabilizing	0.999	D	0.681	prob.neutral	N	0.469282097	None	None	N
E/C	0.9678	likely_pathogenic	0.9584	pathogenic	-0.287	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
E/D	0.6362	likely_pathogenic	0.5353	ambiguous	-1.213	Destabilizing	0.999	D	0.491	neutral	N	0.475523068	None	None	N
E/F	0.9822	likely_pathogenic	0.9702	pathogenic	-0.016	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
E/G	0.7059	likely_pathogenic	0.6504	pathogenic	-1.239	Destabilizing	1.0	D	0.733	prob.delet.	N	0.503288561	None	None	N
E/H	0.936	likely_pathogenic	0.8888	pathogenic	-0.22	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
E/I	0.864	likely_pathogenic	0.8103	pathogenic	0.516	Stabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
E/K	0.8524	likely_pathogenic	0.7785	pathogenic	-0.592	Destabilizing	0.999	D	0.611	neutral	N	0.467912518	None	None	N
E/L	0.8979	likely_pathogenic	0.8462	pathogenic	0.516	Stabilizing	1.0	D	0.808	deleterious	None	None	None	None	N
E/M	0.8824	likely_pathogenic	0.8454	pathogenic	1.109	Stabilizing	1.0	D	0.742	deleterious	None	None	None	None	N
E/N	0.8683	likely_pathogenic	0.8158	pathogenic	-1.166	Destabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	N
E/P	0.9098	likely_pathogenic	0.917	pathogenic	0.105	Stabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
E/Q	0.3943	ambiguous	0.3015	benign	-0.916	Destabilizing	1.0	D	0.631	neutral	N	0.468268139	None	None	N
E/R	0.861	likely_pathogenic	0.7849	pathogenic	-0.401	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
E/S	0.6665	likely_pathogenic	0.5777	pathogenic	-1.685	Destabilizing	0.999	D	0.654	neutral	None	None	None	None	N
E/T	0.7487	likely_pathogenic	0.6461	pathogenic	-1.267	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
E/V	0.7351	likely_pathogenic	0.6484	pathogenic	0.105	Stabilizing	1.0	D	0.791	deleterious	N	0.477866926	None	None	N
E/W	0.993	likely_pathogenic	0.987	pathogenic	0.184	Stabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
E/Y	0.966	likely_pathogenic	0.9449	pathogenic	0.288	Stabilizing	1.0	D	0.782	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.