TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27887	83884;83885;83886	chr2:178562473;178562472;178562471	chr2:179427200;179427199;179427198
N2AB	26246	78961;78962;78963	chr2:178562473;178562472;178562471	chr2:179427200;179427199;179427198
N2A	25319	76180;76181;76182	chr2:178562473;178562472;178562471	chr2:179427200;179427199;179427198
N2B	18822	56689;56690;56691	chr2:178562473;178562472;178562471	chr2:179427200;179427199;179427198
Novex-1	18947	57064;57065;57066	chr2:178562473;178562472;178562471	chr2:179427200;179427199;179427198
Novex-2	19014	57265;57266;57267	chr2:178562473;178562472;178562471	chr2:179427200;179427199;179427198
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: Fn3-91
• Domain position: 25
• Structural Position: 27
• Q(SASA): 0.1611
• 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
P/Q	rs751121559	-2.153	1.0	D	0.843	0.681	None	gnomAD-2.1.1	7.15E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.56E-05	0
P/Q	rs751121559	-2.153	1.0	D	0.843	0.681	None	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
P/Q	rs751121559	-2.153	1.0	D	0.843	0.681	None	gnomAD-4.0.0	6.19908E-06	None	None	None	None	N	None	0	1.66845E-05	None	0	0	None	0	0	7.62967E-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
P/A	0.826	likely_pathogenic	0.8471	pathogenic	-2.005	Highly Destabilizing	0.955	D	0.727	prob.delet.	D	0.5878654720000001	None	None	N
P/C	0.9894	likely_pathogenic	0.9914	pathogenic	-1.395	Destabilizing	1.0	D	0.904	deleterious	None	None	None	None	N
P/D	0.9982	likely_pathogenic	0.9981	pathogenic	-2.468	Highly Destabilizing	0.993	D	0.843	deleterious	None	None	None	None	N
P/E	0.9956	likely_pathogenic	0.9959	pathogenic	-2.37	Highly Destabilizing	0.987	D	0.838	deleterious	None	None	None	None	N
P/F	0.9993	likely_pathogenic	0.9994	pathogenic	-1.393	Destabilizing	1.0	D	0.913	deleterious	None	None	None	None	N
P/G	0.9841	likely_pathogenic	0.9843	pathogenic	-2.439	Highly Destabilizing	0.998	D	0.876	deleterious	None	None	None	None	N
P/H	0.9958	likely_pathogenic	0.9959	pathogenic	-2.129	Highly Destabilizing	1.0	D	0.902	deleterious	None	None	None	None	N
P/I	0.991	likely_pathogenic	0.993	pathogenic	-0.846	Destabilizing	0.998	D	0.894	deleterious	None	None	None	None	N
P/K	0.998	likely_pathogenic	0.9982	pathogenic	-1.753	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
P/L	0.9583	likely_pathogenic	0.9658	pathogenic	-0.846	Destabilizing	0.656	D	0.647	neutral	D	0.600463084	None	None	N
P/M	0.9908	likely_pathogenic	0.9925	pathogenic	-0.633	Destabilizing	0.999	D	0.911	deleterious	None	None	None	None	N
P/N	0.9967	likely_pathogenic	0.9969	pathogenic	-1.745	Destabilizing	0.999	D	0.901	deleterious	None	None	None	None	N
P/Q	0.9937	likely_pathogenic	0.9918	pathogenic	-1.793	Destabilizing	1.0	D	0.843	deleterious	D	0.617491467	None	None	N
P/R	0.9938	likely_pathogenic	0.9945	pathogenic	-1.316	Destabilizing	0.999	D	0.895	deleterious	D	0.601270301	None	None	N
P/S	0.9691	likely_pathogenic	0.971	pathogenic	-2.28	Highly Destabilizing	0.998	D	0.824	deleterious	D	0.560762929	None	None	N
P/T	0.9486	likely_pathogenic	0.9557	pathogenic	-2.064	Highly Destabilizing	0.991	D	0.825	deleterious	D	0.617087858	None	None	N
P/V	0.9709	likely_pathogenic	0.9765	pathogenic	-1.202	Destabilizing	0.991	D	0.848	deleterious	None	None	None	None	N
P/W	0.9996	likely_pathogenic	0.9996	pathogenic	-1.801	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
P/Y	0.999	likely_pathogenic	0.9991	pathogenic	-1.48	Destabilizing	1.0	D	0.919	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.