TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25317	76174;76175;76176	chr2:178570183;178570182;178570181	chr2:179434910;179434909;179434908
N2AB	23676	71251;71252;71253	chr2:178570183;178570182;178570181	chr2:179434910;179434909;179434908
N2A	22749	68470;68471;68472	chr2:178570183;178570182;178570181	chr2:179434910;179434909;179434908
N2B	16252	48979;48980;48981	chr2:178570183;178570182;178570181	chr2:179434910;179434909;179434908
Novex-1	16377	49354;49355;49356	chr2:178570183;178570182;178570181	chr2:179434910;179434909;179434908
Novex-2	16444	49555;49556;49557	chr2:178570183;178570182;178570181	chr2:179434910;179434909;179434908
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-72
• Domain position: 14
• Structural Position: 16
• Q(SASA): 0.2255
• 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
T/P	rs762723439	-0.566	0.971	D	0.473	0.446	0.565793286963	gnomAD-4.0.0	1.59182E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43299E-05	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	0.1373	likely_benign	0.1424	benign	-0.512	Destabilizing	0.014	N	0.215	neutral	N	0.518119016	None	None	N
T/C	0.5292	ambiguous	0.5955	pathogenic	-0.497	Destabilizing	0.994	D	0.455	neutral	None	None	None	None	N
T/D	0.682	likely_pathogenic	0.7391	pathogenic	-1.56	Destabilizing	0.956	D	0.438	neutral	None	None	None	None	N
T/E	0.664	likely_pathogenic	0.6761	pathogenic	-1.532	Destabilizing	0.956	D	0.436	neutral	None	None	None	None	N
T/F	0.5736	likely_pathogenic	0.6041	pathogenic	-0.717	Destabilizing	0.978	D	0.571	neutral	None	None	None	None	N
T/G	0.2254	likely_benign	0.2466	benign	-0.781	Destabilizing	0.754	D	0.443	neutral	None	None	None	None	N
T/H	0.4642	ambiguous	0.5331	ambiguous	-1.264	Destabilizing	0.998	D	0.533	neutral	None	None	None	None	N
T/I	0.7231	likely_pathogenic	0.7513	pathogenic	0.118	Stabilizing	0.942	D	0.474	neutral	N	0.508318672	None	None	N
T/K	0.4309	ambiguous	0.4562	ambiguous	-0.775	Destabilizing	0.956	D	0.442	neutral	None	None	None	None	N
T/L	0.2071	likely_benign	0.229	benign	0.118	Stabilizing	0.754	D	0.414	neutral	None	None	None	None	N
T/M	0.1388	likely_benign	0.1331	benign	0.542	Stabilizing	0.998	D	0.455	neutral	None	None	None	None	N
T/N	0.1812	likely_benign	0.2311	benign	-1.075	Destabilizing	0.942	D	0.447	neutral	N	0.51234505	None	None	N
T/P	0.8366	likely_pathogenic	0.8574	pathogenic	-0.06	Destabilizing	0.971	D	0.473	neutral	D	0.523295828	None	None	N
T/Q	0.3475	ambiguous	0.3677	ambiguous	-1.271	Destabilizing	0.956	D	0.471	neutral	None	None	None	None	N
T/R	0.3634	ambiguous	0.3883	ambiguous	-0.549	Destabilizing	0.956	D	0.476	neutral	None	None	None	None	N
T/S	0.1229	likely_benign	0.1447	benign	-1.075	Destabilizing	0.058	N	0.308	neutral	N	0.459222641	None	None	N
T/V	0.4975	ambiguous	0.534	ambiguous	-0.06	Destabilizing	0.754	D	0.391	neutral	None	None	None	None	N
T/W	0.8839	likely_pathogenic	0.9078	pathogenic	-0.827	Destabilizing	0.998	D	0.563	neutral	None	None	None	None	N
T/Y	0.606	likely_pathogenic	0.6607	pathogenic	-0.472	Destabilizing	0.993	D	0.572	neutral	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.