TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27577	82954;82955;82956	chr2:178563403;178563402;178563401	chr2:179428130;179428129;179428128
N2AB	25936	78031;78032;78033	chr2:178563403;178563402;178563401	chr2:179428130;179428129;179428128
N2A	25009	75250;75251;75252	chr2:178563403;178563402;178563401	chr2:179428130;179428129;179428128
N2B	18512	55759;55760;55761	chr2:178563403;178563402;178563401	chr2:179428130;179428129;179428128
Novex-1	18637	56134;56135;56136	chr2:178563403;178563402;178563401	chr2:179428130;179428129;179428128
Novex-2	18704	56335;56336;56337	chr2:178563403;178563402;178563401	chr2:179428130;179428129;179428128
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: Fn3-89
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.2627
• 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/A	None	None	0.928	N	0.725	0.34	0.321672782286	gnomAD-4.0.0	6.84256E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15931E-05	0
P/T	None	None	0.978	D	0.777	0.405	0.419957187557	gnomAD-4.0.0	6.84256E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99484E-07	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	0.2029	likely_benign	0.178	benign	-1.88	Destabilizing	0.928	D	0.725	prob.delet.	N	0.488739024	None	None	N
P/C	0.7109	likely_pathogenic	0.6698	pathogenic	-1.375	Destabilizing	0.999	D	0.876	deleterious	None	None	None	None	N
P/D	0.9924	likely_pathogenic	0.9878	pathogenic	-2.164	Highly Destabilizing	0.997	D	0.79	deleterious	None	None	None	None	N
P/E	0.9668	likely_pathogenic	0.9508	pathogenic	-2.055	Highly Destabilizing	0.992	D	0.789	deleterious	None	None	None	None	N
P/F	0.8677	likely_pathogenic	0.8151	pathogenic	-1.296	Destabilizing	0.991	D	0.891	deleterious	None	None	None	None	N
P/G	0.8297	likely_pathogenic	0.7832	pathogenic	-2.325	Highly Destabilizing	0.992	D	0.816	deleterious	None	None	None	None	N
P/H	0.9099	likely_pathogenic	0.8621	pathogenic	-2.068	Highly Destabilizing	0.999	D	0.854	deleterious	None	None	None	None	N
P/I	0.3937	ambiguous	0.3483	ambiguous	-0.695	Destabilizing	0.968	D	0.84	deleterious	None	None	None	None	N
P/K	0.9636	likely_pathogenic	0.943	pathogenic	-1.589	Destabilizing	0.992	D	0.794	deleterious	None	None	None	None	N
P/L	0.2127	likely_benign	0.1875	benign	-0.695	Destabilizing	0.085	N	0.675	neutral	N	0.44955186	None	None	N
P/M	0.5871	likely_pathogenic	0.5397	ambiguous	-0.577	Destabilizing	0.996	D	0.866	deleterious	None	None	None	None	N
P/N	0.9686	likely_pathogenic	0.9508	pathogenic	-1.607	Destabilizing	0.997	D	0.848	deleterious	None	None	None	None	N
P/Q	0.8756	likely_pathogenic	0.8252	pathogenic	-1.619	Destabilizing	0.996	D	0.805	deleterious	D	0.538963639	None	None	N
P/R	0.9184	likely_pathogenic	0.8774	pathogenic	-1.251	Destabilizing	0.989	D	0.845	deleterious	D	0.538963639	None	None	N
P/S	0.6903	likely_pathogenic	0.6126	pathogenic	-2.191	Highly Destabilizing	0.989	D	0.784	deleterious	N	0.520605895	None	None	N
P/T	0.4263	ambiguous	0.3556	ambiguous	-1.955	Destabilizing	0.978	D	0.777	deleterious	D	0.527100355	None	None	N
P/V	0.2722	likely_benign	0.2353	benign	-1.059	Destabilizing	0.968	D	0.789	deleterious	None	None	None	None	N
P/W	0.9691	likely_pathogenic	0.95	pathogenic	-1.707	Destabilizing	0.999	D	0.847	deleterious	None	None	None	None	N
P/Y	0.9439	likely_pathogenic	0.9127	pathogenic	-1.353	Destabilizing	0.998	D	0.893	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.