TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21366	64321;64322;64323	chr2:178586805;178586804;178586803	chr2:179451532;179451531;179451530
N2AB	19725	59398;59399;59400	chr2:178586805;178586804;178586803	chr2:179451532;179451531;179451530
N2A	18798	56617;56618;56619	chr2:178586805;178586804;178586803	chr2:179451532;179451531;179451530
N2B	12301	37126;37127;37128	chr2:178586805;178586804;178586803	chr2:179451532;179451531;179451530
Novex-1	12426	37501;37502;37503	chr2:178586805;178586804;178586803	chr2:179451532;179451531;179451530
Novex-2	12493	37702;37703;37704	chr2:178586805;178586804;178586803	chr2:179451532;179451531;179451530
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: Fn3-43
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.4732
• 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
E/K	rs2049080412	None	0.546	N	0.535	0.291	0.277730125212	gnomAD-4.0.0	3.21062E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.73947E-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	0.1557	likely_benign	0.1372	benign	-0.722	Destabilizing	0.004	N	0.304	neutral	N	0.456944766	None	None	I
E/C	0.8446	likely_pathogenic	0.8355	pathogenic	-0.057	Destabilizing	0.992	D	0.865	deleterious	None	None	None	None	I
E/D	0.5233	ambiguous	0.4455	ambiguous	-0.482	Destabilizing	0.709	D	0.478	neutral	N	0.517206578	None	None	I
E/F	0.8617	likely_pathogenic	0.8267	pathogenic	-0.645	Destabilizing	0.848	D	0.855	deleterious	None	None	None	None	I
E/G	0.4416	ambiguous	0.3816	ambiguous	-0.933	Destabilizing	0.376	N	0.607	neutral	N	0.464564247	None	None	I
E/H	0.7663	likely_pathogenic	0.7082	pathogenic	-0.632	Destabilizing	0.992	D	0.548	neutral	None	None	None	None	I
E/I	0.3459	ambiguous	0.3021	benign	-0.188	Destabilizing	0.491	N	0.6	neutral	None	None	None	None	I
E/K	0.2604	likely_benign	0.2193	benign	0.185	Stabilizing	0.546	D	0.535	neutral	N	0.410212399	None	None	I
E/L	0.4782	ambiguous	0.4246	ambiguous	-0.188	Destabilizing	0.444	N	0.619	neutral	None	None	None	None	I
E/M	0.4906	ambiguous	0.4486	ambiguous	0.159	Stabilizing	0.955	D	0.809	deleterious	None	None	None	None	I
E/N	0.6716	likely_pathogenic	0.603	pathogenic	-0.142	Destabilizing	0.919	D	0.555	neutral	None	None	None	None	I
E/P	0.3489	ambiguous	0.3068	benign	-0.346	Destabilizing	0.919	D	0.606	neutral	None	None	None	None	I
E/Q	0.1828	likely_benign	0.1595	benign	-0.129	Destabilizing	0.895	D	0.524	neutral	N	0.498351459	None	None	I
E/R	0.4255	ambiguous	0.3645	ambiguous	0.292	Stabilizing	0.919	D	0.548	neutral	None	None	None	None	I
E/S	0.3963	ambiguous	0.3419	ambiguous	-0.325	Destabilizing	0.444	N	0.482	neutral	None	None	None	None	I
E/T	0.3605	ambiguous	0.3133	benign	-0.148	Destabilizing	0.615	D	0.648	neutral	None	None	None	None	I
E/V	0.1865	likely_benign	0.1702	benign	-0.346	Destabilizing	0.004	N	0.391	neutral	N	0.379425345	None	None	I
E/W	0.9771	likely_pathogenic	0.9678	pathogenic	-0.451	Destabilizing	0.992	D	0.879	deleterious	None	None	None	None	I
E/Y	0.8254	likely_pathogenic	0.7737	pathogenic	-0.392	Destabilizing	0.919	D	0.855	deleterious	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.