TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17456	52591;52592;52593	chr2:178608645;178608644;178608643	chr2:179473372;179473371;179473370
N2AB	15815	47668;47669;47670	chr2:178608645;178608644;178608643	chr2:179473372;179473371;179473370
N2A	14888	44887;44888;44889	chr2:178608645;178608644;178608643	chr2:179473372;179473371;179473370
N2B	8391	25396;25397;25398	chr2:178608645;178608644;178608643	chr2:179473372;179473371;179473370
Novex-1	8516	25771;25772;25773	chr2:178608645;178608644;178608643	chr2:179473372;179473371;179473370
Novex-2	8583	25972;25973;25974	chr2:178608645;178608644;178608643	chr2:179473372;179473371;179473370
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-14
• Domain position: 88
• Structural Position: 120
• Q(SASA): 0.2862
• 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
P/Q	None	None	0.998	D	0.654	0.444	0.445910236696	gnomAD-4.0.0	1.5959E-06	None	None	None	None	I	None	0	0	None	0	2.79658E-05	None	0	0	0	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
P/A	0.0877	likely_benign	0.0897	benign	-1.568	Destabilizing	0.543	D	0.449	neutral	N	0.487938876	None	None	I
P/C	0.5888	likely_pathogenic	0.6098	pathogenic	-0.847	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	I
P/D	0.886	likely_pathogenic	0.9086	pathogenic	-1.624	Destabilizing	0.999	D	0.583	neutral	None	None	None	None	I
P/E	0.8048	likely_pathogenic	0.8328	pathogenic	-1.64	Destabilizing	0.998	D	0.62	neutral	None	None	None	None	I
P/F	0.6537	likely_pathogenic	0.7261	pathogenic	-1.229	Destabilizing	0.999	D	0.749	deleterious	None	None	None	None	I
P/G	0.4459	ambiguous	0.4713	ambiguous	-1.861	Destabilizing	0.992	D	0.587	neutral	None	None	None	None	I
P/H	0.5377	ambiguous	0.5727	pathogenic	-1.438	Destabilizing	0.661	D	0.577	neutral	None	None	None	None	I
P/I	0.6797	likely_pathogenic	0.7551	pathogenic	-0.859	Destabilizing	0.999	D	0.733	prob.delet.	None	None	None	None	I
P/K	0.9266	likely_pathogenic	0.9367	pathogenic	-1.434	Destabilizing	0.999	D	0.607	neutral	None	None	None	None	I
P/L	0.5244	ambiguous	0.5975	pathogenic	-0.859	Destabilizing	0.997	D	0.679	prob.neutral	N	0.513538322	None	None	I
P/M	0.7212	likely_pathogenic	0.7708	pathogenic	-0.561	Destabilizing	1.0	D	0.702	prob.neutral	None	None	None	None	I
P/N	0.8271	likely_pathogenic	0.8532	pathogenic	-1.128	Destabilizing	0.998	D	0.675	neutral	None	None	None	None	I
P/Q	0.6858	likely_pathogenic	0.7146	pathogenic	-1.338	Destabilizing	0.998	D	0.654	neutral	D	0.533417004	None	None	I
P/R	0.8504	likely_pathogenic	0.8601	pathogenic	-0.821	Destabilizing	0.998	D	0.674	neutral	N	0.521389135	None	None	I
P/S	0.2113	likely_benign	0.2195	benign	-1.552	Destabilizing	0.978	D	0.567	neutral	N	0.50565151	None	None	I
P/T	0.3703	ambiguous	0.412	ambiguous	-1.478	Destabilizing	0.997	D	0.613	neutral	D	0.533163514	None	None	I
P/V	0.4696	ambiguous	0.54	ambiguous	-1.062	Destabilizing	0.998	D	0.615	neutral	None	None	None	None	I
P/W	0.832	likely_pathogenic	0.8663	pathogenic	-1.424	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	I
P/Y	0.6739	likely_pathogenic	0.7411	pathogenic	-1.18	Destabilizing	0.998	D	0.743	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.