TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7353	22282;22283;22284	chr2:178722842;178722841;178722840	chr2:179587569;179587568;179587567
N2AB	7036	21331;21332;21333	chr2:178722842;178722841;178722840	chr2:179587569;179587568;179587567
N2A	6109	18550;18551;18552	chr2:178722842;178722841;178722840	chr2:179587569;179587568;179587567
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: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-58
• Domain position: 31
• Structural Position: 45
• Q(SASA): 0.4589
• 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
T/R	None	None	0.669	N	0.448	0.259	0.647989276156	gnomAD-4.0.0	1.59249E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86013E-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
T/A	0.0751	likely_benign	0.0819	benign	-0.715	Destabilizing	0.625	D	0.412	neutral	N	0.512798915	None	None	I
T/C	0.426	ambiguous	0.4907	ambiguous	-0.542	Destabilizing	0.998	D	0.519	neutral	None	None	None	None	I
T/D	0.3554	ambiguous	0.4082	ambiguous	0.261	Stabilizing	0.016	N	0.256	neutral	None	None	None	None	I
T/E	0.263	likely_benign	0.2954	benign	0.254	Stabilizing	0.525	D	0.433	neutral	None	None	None	None	I
T/F	0.1867	likely_benign	0.2214	benign	-1.0	Destabilizing	0.991	D	0.584	neutral	None	None	None	None	I
T/G	0.2229	likely_benign	0.2487	benign	-0.926	Destabilizing	0.842	D	0.483	neutral	None	None	None	None	I
T/H	0.2023	likely_benign	0.232	benign	-1.067	Destabilizing	0.974	D	0.567	neutral	None	None	None	None	I
T/I	0.1177	likely_benign	0.1412	benign	-0.255	Destabilizing	0.966	D	0.565	neutral	D	0.524536061	None	None	I
T/K	0.137	likely_benign	0.1544	benign	-0.452	Destabilizing	0.022	N	0.202	neutral	N	0.438319799	None	None	I
T/L	0.0902	likely_benign	0.0967	benign	-0.255	Destabilizing	0.842	D	0.454	neutral	None	None	None	None	I
T/M	0.0805	likely_benign	0.0885	benign	-0.221	Destabilizing	0.991	D	0.538	neutral	None	None	None	None	I
T/N	0.1157	likely_benign	0.1249	benign	-0.447	Destabilizing	0.842	D	0.355	neutral	None	None	None	None	I
T/P	0.2615	likely_benign	0.3235	benign	-0.377	Destabilizing	0.891	D	0.535	neutral	N	0.4994194	None	None	I
T/Q	0.1813	likely_benign	0.1971	benign	-0.539	Destabilizing	0.067	N	0.272	neutral	None	None	None	None	I
T/R	0.1143	likely_benign	0.1262	benign	-0.233	Destabilizing	0.669	D	0.448	neutral	N	0.475088676	None	None	I
T/S	0.1	likely_benign	0.1073	benign	-0.749	Destabilizing	0.625	D	0.401	neutral	N	0.457038846	None	None	I
T/V	0.1079	likely_benign	0.1196	benign	-0.377	Destabilizing	0.915	D	0.357	neutral	None	None	None	None	I
T/W	0.4947	ambiguous	0.5763	pathogenic	-0.969	Destabilizing	0.998	D	0.59	neutral	None	None	None	None	I
T/Y	0.2426	likely_benign	0.2922	benign	-0.694	Destabilizing	0.991	D	0.588	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.