TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32569	97930;97931;97932	chr2:178541372;178541371;178541370	chr2:179406099;179406098;179406097
N2AB	30928	93007;93008;93009	chr2:178541372;178541371;178541370	chr2:179406099;179406098;179406097
N2A	30001	90226;90227;90228	chr2:178541372;178541371;178541370	chr2:179406099;179406098;179406097
N2B	23504	70735;70736;70737	chr2:178541372;178541371;178541370	chr2:179406099;179406098;179406097
Novex-1	23629	71110;71111;71112	chr2:178541372;178541371;178541370	chr2:179406099;179406098;179406097
Novex-2	23696	71311;71312;71313	chr2:178541372;178541371;178541370	chr2:179406099;179406098;179406097
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: Fn3-125
• Domain position: 71
• Structural Position: 103
• Q(SASA): 0.3307
• 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/Q	rs760105762	-0.373	1.0	N	0.637	0.314	0.398283496042	gnomAD-2.1.1	4.2E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.31E-06	0
E/Q	rs760105762	-0.373	1.0	N	0.637	0.314	0.398283496042	gnomAD-4.0.0	1.37505E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80484E-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	0.2053	likely_benign	0.2155	benign	-0.882	Destabilizing	0.999	D	0.706	prob.neutral	N	0.511459616	None	None	N
E/C	0.849	likely_pathogenic	0.8516	pathogenic	-0.581	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
E/D	0.4603	ambiguous	0.4499	ambiguous	-1.464	Destabilizing	0.999	D	0.492	neutral	N	0.50384021	None	None	N
E/F	0.8541	likely_pathogenic	0.8597	pathogenic	-0.322	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
E/G	0.4113	ambiguous	0.43	ambiguous	-1.315	Destabilizing	1.0	D	0.764	deleterious	N	0.483538465	None	None	N
E/H	0.7176	likely_pathogenic	0.7451	pathogenic	-0.642	Destabilizing	1.0	D	0.68	prob.neutral	None	None	None	None	N
E/I	0.4298	ambiguous	0.4703	ambiguous	0.334	Stabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
E/K	0.3876	ambiguous	0.4541	ambiguous	-1.303	Destabilizing	0.999	D	0.624	neutral	N	0.44650406	None	None	N
E/L	0.4692	ambiguous	0.496	ambiguous	0.334	Stabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
E/M	0.5009	ambiguous	0.533	ambiguous	0.927	Stabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
E/N	0.6104	likely_pathogenic	0.6253	pathogenic	-1.653	Destabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	N
E/P	0.6938	likely_pathogenic	0.6673	pathogenic	-0.052	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
E/Q	0.178	likely_benign	0.2016	benign	-1.371	Destabilizing	1.0	D	0.637	neutral	N	0.472786585	None	None	N
E/R	0.4828	ambiguous	0.5435	ambiguous	-1.114	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	N
E/S	0.3651	ambiguous	0.386	ambiguous	-2.165	Highly Destabilizing	0.999	D	0.671	neutral	None	None	None	None	N
E/T	0.3088	likely_benign	0.3421	ambiguous	-1.789	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
E/V	0.255	likely_benign	0.2881	benign	-0.052	Destabilizing	1.0	D	0.795	deleterious	N	0.513230485	None	None	N
E/W	0.9432	likely_pathogenic	0.9506	pathogenic	-0.325	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
E/Y	0.789	likely_pathogenic	0.8021	pathogenic	-0.139	Destabilizing	1.0	D	0.777	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.