TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19772	59539;59540;59541	chr2:178592805;178592804;178592803	chr2:179457532;179457531;179457530
N2AB	18131	54616;54617;54618	chr2:178592805;178592804;178592803	chr2:179457532;179457531;179457530
N2A	17204	51835;51836;51837	chr2:178592805;178592804;178592803	chr2:179457532;179457531;179457530
N2B	10707	32344;32345;32346	chr2:178592805;178592804;178592803	chr2:179457532;179457531;179457530
Novex-1	10832	32719;32720;32721	chr2:178592805;178592804;178592803	chr2:179457532;179457531;179457530
Novex-2	10899	32920;32921;32922	chr2:178592805;178592804;178592803	chr2:179457532;179457531;179457530
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCG
• RefSeq wild type template codon: GGC
• Domain: Fn3-31
• Domain position: 93
• Structural Position: 124
• Q(SASA): 0.5988
• Predicted PPI site: I

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/L	rs72646840	-0.027	0.913	N	0.483	0.195	None	gnomAD-2.1.1	1.06161E-03	None	None	None	None	I	None	1.04967E-02	5.66572E-04	None	0	0	None	3.27E-05	None	0	1.487E-04	4.21467E-04
P/L	rs72646840	-0.027	0.913	N	0.483	0.195	None	gnomAD-3.1.2	3.06381E-03	None	None	None	None	I	None	1.03538E-02	8.51566E-04	0	0	0	None	0	0	2.79387E-04	2.07297E-04	1.91205E-03
P/L	rs72646840	-0.027	0.913	N	0.483	0.195	None	1000 genomes	2.39617E-03	None	None	None	None	I	None	7.6E-03	2.9E-03	None	None	0	0	None	None	None	0	None
P/L	rs72646840	-0.027	0.913	N	0.483	0.195	None	gnomAD-4.0.0	6.8734E-04	None	None	None	None	I	None	1.07194E-02	6.66867E-04	None	0	0	None	0	1.6518E-04	1.67851E-04	6.58906E-05	9.60461E-04
P/Q	None	None	0.943	N	0.479	0.166	0.340753184043	gnomAD-4.0.0	2.05304E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	4.97051E-05
P/R	rs72646840	None	0.006	N	0.331	0.184	0.255270683199	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
P/R	rs72646840	None	0.006	N	0.331	0.184	0.255270683199	gnomAD-4.0.0	6.57462E-06	None	None	None	None	I	None	2.41336E-05	0	None	0	0	None	0	0	0	0	0
P/T	rs773420166	-0.179	0.651	N	0.45	0.186	0.308904156042	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
P/T	rs773420166	-0.179	0.651	N	0.45	0.186	0.308904156042	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
P/T	rs773420166	-0.179	0.651	N	0.45	0.186	0.308904156042	gnomAD-4.0.0	1.8595E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.54319E-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	0.0898	likely_benign	0.0872	benign	-0.466	Destabilizing	0.435	N	0.357	neutral	N	0.498676746	None	None	I
P/C	0.5395	ambiguous	0.5138	ambiguous	-0.613	Destabilizing	0.995	D	0.548	neutral	None	None	None	None	I
P/D	0.4149	ambiguous	0.3942	ambiguous	-0.778	Destabilizing	0.712	D	0.463	neutral	None	None	None	None	I
P/E	0.2758	likely_benign	0.2501	benign	-0.893	Destabilizing	0.553	D	0.382	neutral	None	None	None	None	I
P/F	0.5426	ambiguous	0.5309	ambiguous	-0.768	Destabilizing	0.982	D	0.501	neutral	None	None	None	None	I
P/G	0.2782	likely_benign	0.2808	benign	-0.571	Destabilizing	0.712	D	0.381	neutral	None	None	None	None	I
P/H	0.2154	likely_benign	0.2084	benign	-0.198	Destabilizing	0.946	D	0.423	neutral	None	None	None	None	I
P/I	0.3241	likely_benign	0.3119	benign	-0.331	Destabilizing	0.946	D	0.587	neutral	None	None	None	None	I
P/K	0.2444	likely_benign	0.232	benign	-0.613	Destabilizing	0.003	N	0.154	neutral	None	None	None	None	I
P/L	0.1323	likely_benign	0.135	benign	-0.331	Destabilizing	0.913	D	0.483	neutral	N	0.45869799	None	None	I
P/M	0.2847	likely_benign	0.2844	benign	-0.492	Destabilizing	0.995	D	0.429	neutral	None	None	None	None	I
P/N	0.2981	likely_benign	0.2999	benign	-0.331	Destabilizing	0.897	D	0.474	neutral	None	None	None	None	I
P/Q	0.1555	likely_benign	0.1499	benign	-0.592	Destabilizing	0.943	D	0.479	neutral	N	0.461993353	None	None	I
P/R	0.1866	likely_benign	0.171	benign	-0.065	Destabilizing	0.006	N	0.331	neutral	N	0.490307979	None	None	I
P/S	0.1253	likely_benign	0.1232	benign	-0.561	Destabilizing	0.651	D	0.377	neutral	N	0.433779905	None	None	I
P/T	0.1054	likely_benign	0.1031	benign	-0.591	Destabilizing	0.651	D	0.45	neutral	N	0.474895809	None	None	I
P/V	0.2133	likely_benign	0.2033	benign	-0.345	Destabilizing	0.946	D	0.473	neutral	None	None	None	None	I
P/W	0.6599	likely_pathogenic	0.6477	pathogenic	-0.864	Destabilizing	0.995	D	0.596	neutral	None	None	None	None	I
P/Y	0.498	ambiguous	0.4993	ambiguous	-0.581	Destabilizing	0.982	D	0.524	neutral	None	None	None	None	I

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.