TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6505	19738;19739;19740	chr2:178728311;178728310;178728309	chr2:179593038;179593037;179593036
N2AB	6188	18787;18788;18789	chr2:178728311;178728310;178728309	chr2:179593038;179593037;179593036
N2A	5261	16006;16007;16008	chr2:178728311;178728310;178728309	chr2:179593038;179593037;179593036
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: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-49
• Domain position: 25
• Structural Position: 38
• Q(SASA): 0.3964
• 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
S/F	rs1414011435	-0.866	0.971	N	0.65	0.466	0.791178816626	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.96E-06	0
S/F	rs1414011435	-0.866	0.971	N	0.65	0.466	0.791178816626	gnomAD-4.0.0	1.593E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86038E-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
S/A	0.0942	likely_benign	0.0965	benign	-0.498	Destabilizing	0.006	N	0.173	neutral	N	0.511798838	None	None	N
S/C	0.2667	likely_benign	0.2507	benign	-0.334	Destabilizing	0.992	D	0.573	neutral	D	0.535503005	None	None	N
S/D	0.6195	likely_pathogenic	0.5565	ambiguous	0.322	Stabilizing	0.978	D	0.502	neutral	None	None	None	None	N
S/E	0.6699	likely_pathogenic	0.6295	pathogenic	0.257	Stabilizing	0.86	D	0.479	neutral	None	None	None	None	N
S/F	0.2723	likely_benign	0.2291	benign	-1.0	Destabilizing	0.971	D	0.65	neutral	N	0.494179161	None	None	N
S/G	0.1934	likely_benign	0.1811	benign	-0.65	Destabilizing	0.559	D	0.448	neutral	None	None	None	None	N
S/H	0.5533	ambiguous	0.509	ambiguous	-1.175	Destabilizing	0.998	D	0.573	neutral	None	None	None	None	N
S/I	0.2971	likely_benign	0.245	benign	-0.222	Destabilizing	0.956	D	0.639	neutral	None	None	None	None	N
S/K	0.8344	likely_pathogenic	0.8147	pathogenic	-0.384	Destabilizing	0.86	D	0.476	neutral	None	None	None	None	N
S/L	0.1302	likely_benign	0.1249	benign	-0.222	Destabilizing	0.754	D	0.519	neutral	None	None	None	None	N
S/M	0.3165	likely_benign	0.2879	benign	0.045	Stabilizing	0.998	D	0.575	neutral	None	None	None	None	N
S/N	0.3013	likely_benign	0.2572	benign	-0.184	Destabilizing	0.978	D	0.52	neutral	None	None	None	None	N
S/P	0.9066	likely_pathogenic	0.8833	pathogenic	-0.283	Destabilizing	0.971	D	0.606	neutral	N	0.512283416	None	None	N
S/Q	0.6794	likely_pathogenic	0.6514	pathogenic	-0.406	Destabilizing	0.978	D	0.567	neutral	None	None	None	None	N
S/R	0.7332	likely_pathogenic	0.7041	pathogenic	-0.257	Destabilizing	0.956	D	0.611	neutral	None	None	None	None	N
S/T	0.114	likely_benign	0.1014	benign	-0.304	Destabilizing	0.822	D	0.419	neutral	D	0.530325883	None	None	N
S/V	0.2926	likely_benign	0.2596	benign	-0.283	Destabilizing	0.754	D	0.519	neutral	None	None	None	None	N
S/W	0.4759	ambiguous	0.4213	ambiguous	-0.962	Destabilizing	0.998	D	0.668	neutral	None	None	None	None	N
S/Y	0.2856	likely_benign	0.2593	benign	-0.681	Destabilizing	0.99	D	0.641	neutral	N	0.518034164	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.