TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5769	17530;17531;17532	chr2:178731461;178731460;178731459	chr2:179596188;179596187;179596186
N2AB	5452	16579;16580;16581	chr2:178731461;178731460;178731459	chr2:179596188;179596187;179596186
N2A	4525	13798;13799;13800	chr2:178731461;178731460;178731459	chr2:179596188;179596187;179596186
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-41
• Domain position: 40
• Structural Position: 56
• Q(SASA): 0.8263
• 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	rs756902467	-0.167	0.625	D	0.347	0.279	0.430010490656	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
E/A	rs756902467	-0.167	0.625	D	0.347	0.279	0.430010490656	gnomAD-4.0.0	6.8423E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15937E-05	0
E/G	None	None	0.801	N	0.373	0.436	0.534093007224	gnomAD-4.0.0	6.8423E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99467E-07	0	0
E/K	None	None	0.051	N	0.237	0.188	0.311079019809	gnomAD-4.0.0	1.36845E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79893E-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	0.142	likely_benign	0.1348	benign	-0.415	Destabilizing	0.625	D	0.347	neutral	D	0.532712828	None	None	N
E/C	0.7794	likely_pathogenic	0.7605	pathogenic	-0.113	Destabilizing	0.998	D	0.354	neutral	None	None	None	None	N
E/D	0.1106	likely_benign	0.1115	benign	-0.427	Destabilizing	0.005	N	0.209	neutral	N	0.488010188	None	None	N
E/F	0.5869	likely_pathogenic	0.5511	ambiguous	-0.216	Destabilizing	0.904	D	0.361	neutral	None	None	None	None	N
E/G	0.178	likely_benign	0.1689	benign	-0.637	Destabilizing	0.801	D	0.373	neutral	N	0.509156317	None	None	N
E/H	0.3815	ambiguous	0.3677	ambiguous	-0.011	Destabilizing	0.037	N	0.221	neutral	None	None	None	None	N
E/I	0.2273	likely_benign	0.201	benign	0.141	Stabilizing	0.974	D	0.369	neutral	None	None	None	None	N
E/K	0.1195	likely_benign	0.1144	benign	0.219	Stabilizing	0.051	N	0.237	neutral	N	0.491807567	None	None	N
E/L	0.3044	likely_benign	0.2852	benign	0.141	Stabilizing	0.842	D	0.39	neutral	None	None	None	None	N
E/M	0.3462	ambiguous	0.3224	benign	0.217	Stabilizing	0.998	D	0.339	neutral	None	None	None	None	N
E/N	0.2024	likely_benign	0.1915	benign	-0.141	Destabilizing	0.728	D	0.333	neutral	None	None	None	None	N
E/P	0.3906	ambiguous	0.3556	ambiguous	-0.024	Destabilizing	0.974	D	0.373	neutral	None	None	None	None	N
E/Q	0.1372	likely_benign	0.1368	benign	-0.093	Destabilizing	0.801	D	0.391	neutral	N	0.51126012	None	None	N
E/R	0.2122	likely_benign	0.2021	benign	0.468	Stabilizing	0.728	D	0.365	neutral	None	None	None	None	N
E/S	0.1887	likely_benign	0.1804	benign	-0.309	Destabilizing	0.842	D	0.329	neutral	None	None	None	None	N
E/T	0.1863	likely_benign	0.1703	benign	-0.129	Destabilizing	0.842	D	0.396	neutral	None	None	None	None	N
E/V	0.1485	likely_benign	0.1353	benign	-0.024	Destabilizing	0.801	D	0.363	neutral	N	0.509972041	None	None	N
E/W	0.828	likely_pathogenic	0.8173	pathogenic	-0.045	Destabilizing	0.998	D	0.348	neutral	None	None	None	None	N
E/Y	0.4644	ambiguous	0.4343	ambiguous	0.03	Stabilizing	0.067	N	0.268	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.