TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5456	16591;16592;16593	chr2:178732695;178732694;178732693	chr2:179597422;179597421;179597420
N2AB	5139	15640;15641;15642	chr2:178732695;178732694;178732693	chr2:179597422;179597421;179597420
N2A	4212	12859;12860;12861	chr2:178732695;178732694;178732693	chr2:179597422;179597421;179597420
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: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Ig-38
• Domain position: 7
• Structural Position: 8
• Q(SASA): 0.2505
• 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
P/A	None	None	0.992	N	0.603	0.465	0.385578977469	gnomAD-4.0.0	2.07547E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.71771E-06	0	0
P/L	rs876658041	0.323	0.999	N	0.863	0.43	0.629443713816	gnomAD-2.1.1	4.27E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.33E-06	0
P/L	rs876658041	0.323	0.999	N	0.863	0.43	0.629443713816	gnomAD-4.0.0	1.63298E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.92422E-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
P/A	0.2026	likely_benign	0.2152	benign	-1.441	Destabilizing	0.992	D	0.603	neutral	N	0.511958614	None	None	N
P/C	0.8653	likely_pathogenic	0.8792	pathogenic	-1.217	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
P/D	0.9502	likely_pathogenic	0.9593	pathogenic	-0.604	Destabilizing	0.999	D	0.789	deleterious	None	None	None	None	N
P/E	0.8533	likely_pathogenic	0.8698	pathogenic	-0.563	Destabilizing	0.999	D	0.79	deleterious	None	None	None	None	N
P/F	0.8864	likely_pathogenic	0.9054	pathogenic	-1.048	Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
P/G	0.778	likely_pathogenic	0.7878	pathogenic	-1.801	Destabilizing	0.997	D	0.739	prob.delet.	None	None	None	None	N
P/H	0.854	likely_pathogenic	0.872	pathogenic	-1.29	Destabilizing	1.0	D	0.857	deleterious	D	0.524746951	None	None	N
P/I	0.5118	ambiguous	0.5317	ambiguous	-0.542	Destabilizing	1.0	D	0.892	deleterious	None	None	None	None	N
P/K	0.928	likely_pathogenic	0.9364	pathogenic	-0.937	Destabilizing	0.999	D	0.787	deleterious	None	None	None	None	N
P/L	0.2159	likely_benign	0.2504	benign	-0.542	Destabilizing	0.999	D	0.863	deleterious	N	0.492868281	None	None	N
P/M	0.5961	likely_pathogenic	0.6233	pathogenic	-0.577	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
P/N	0.9183	likely_pathogenic	0.9309	pathogenic	-0.775	Destabilizing	0.999	D	0.853	deleterious	None	None	None	None	N
P/Q	0.783	likely_pathogenic	0.7965	pathogenic	-0.857	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
P/R	0.8466	likely_pathogenic	0.8614	pathogenic	-0.615	Destabilizing	0.999	D	0.863	deleterious	D	0.524239972	None	None	N
P/S	0.6776	likely_pathogenic	0.695	pathogenic	-1.498	Destabilizing	0.957	D	0.421	neutral	N	0.497488437	None	None	N
P/T	0.3943	ambiguous	0.4296	ambiguous	-1.322	Destabilizing	0.999	D	0.776	deleterious	N	0.499134278	None	None	N
P/V	0.398	ambiguous	0.4158	ambiguous	-0.807	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
P/W	0.9634	likely_pathogenic	0.971	pathogenic	-1.189	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
P/Y	0.9278	likely_pathogenic	0.9423	pathogenic	-0.873	Destabilizing	1.0	D	0.893	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.