TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17012	51259;51260;51261	chr2:178611095;178611094;178611093	chr2:179475822;179475821;179475820
N2AB	15371	46336;46337;46338	chr2:178611095;178611094;178611093	chr2:179475822;179475821;179475820
N2A	14444	43555;43556;43557	chr2:178611095;178611094;178611093	chr2:179475822;179475821;179475820
N2B	7947	24064;24065;24066	chr2:178611095;178611094;178611093	chr2:179475822;179475821;179475820
Novex-1	8072	24439;24440;24441	chr2:178611095;178611094;178611093	chr2:179475822;179475821;179475820
Novex-2	8139	24640;24641;24642	chr2:178611095;178611094;178611093	chr2:179475822;179475821;179475820
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-111
• Domain position: 58
• Structural Position: 138
• Q(SASA): 0.0869
• 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
L/P	None	None	1.0	D	0.905	0.883	0.911962184262	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
L/A	0.8608	likely_pathogenic	0.8747	pathogenic	-2.631	Highly Destabilizing	0.999	D	0.764	deleterious	None	None	None	None	N
L/C	0.8092	likely_pathogenic	0.8288	pathogenic	-2.121	Highly Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	N
L/D	0.9991	likely_pathogenic	0.9991	pathogenic	-3.35	Highly Destabilizing	1.0	D	0.906	deleterious	None	None	None	None	N
L/E	0.9922	likely_pathogenic	0.9922	pathogenic	-3.03	Highly Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
L/F	0.272	likely_benign	0.3139	benign	-1.586	Destabilizing	1.0	D	0.823	deleterious	D	0.577055508	None	None	N
L/G	0.9805	likely_pathogenic	0.9809	pathogenic	-3.261	Highly Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
L/H	0.9709	likely_pathogenic	0.9704	pathogenic	-2.953	Highly Destabilizing	1.0	D	0.886	deleterious	D	0.775276358	None	None	N
L/I	0.1238	likely_benign	0.1426	benign	-0.753	Destabilizing	0.999	D	0.655	neutral	D	0.555891142	None	None	N
L/K	0.9858	likely_pathogenic	0.9841	pathogenic	-2.141	Highly Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
L/M	0.1927	likely_benign	0.2121	benign	-0.94	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
L/N	0.9941	likely_pathogenic	0.9948	pathogenic	-2.804	Highly Destabilizing	1.0	D	0.906	deleterious	None	None	None	None	N
L/P	0.9949	likely_pathogenic	0.9943	pathogenic	-1.367	Destabilizing	1.0	D	0.905	deleterious	D	0.775276358	None	None	N
L/Q	0.9634	likely_pathogenic	0.9628	pathogenic	-2.473	Highly Destabilizing	1.0	D	0.914	deleterious	None	None	None	None	N
L/R	0.9697	likely_pathogenic	0.9644	pathogenic	-2.163	Highly Destabilizing	1.0	D	0.905	deleterious	D	0.739025159	None	None	N
L/S	0.9805	likely_pathogenic	0.9829	pathogenic	-3.444	Highly Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	N
L/T	0.9177	likely_pathogenic	0.9308	pathogenic	-2.946	Highly Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
L/V	0.1733	likely_benign	0.1893	benign	-1.367	Destabilizing	0.999	D	0.66	neutral	D	0.628873357	None	None	N
L/W	0.8288	likely_pathogenic	0.8247	pathogenic	-2.019	Highly Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
L/Y	0.8802	likely_pathogenic	0.888	pathogenic	-1.742	Destabilizing	1.0	D	0.878	deleterious	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.