TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29761	89506;89507;89508	chr2:178553724;178553723;178553722	chr2:179418451;179418450;179418449
N2AB	28120	84583;84584;84585	chr2:178553724;178553723;178553722	chr2:179418451;179418450;179418449
N2A	27193	81802;81803;81804	chr2:178553724;178553723;178553722	chr2:179418451;179418450;179418449
N2B	20696	62311;62312;62313	chr2:178553724;178553723;178553722	chr2:179418451;179418450;179418449
Novex-1	20821	62686;62687;62688	chr2:178553724;178553723;178553722	chr2:179418451;179418450;179418449
Novex-2	20888	62887;62888;62889	chr2:178553724;178553723;178553722	chr2:179418451;179418450;179418449
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-105
• Domain position: 28
• Structural Position: 30
• Q(SASA): 0.2879
• 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
D/G	None	None	1.0	N	0.727	0.563	0.412064437402	gnomAD-4.0.0	6.84273E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99518E-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
D/A	0.8437	likely_pathogenic	0.8152	pathogenic	-0.706	Destabilizing	1.0	D	0.76	deleterious	N	0.481372418	None	None	I
D/C	0.9518	likely_pathogenic	0.9461	pathogenic	-0.211	Destabilizing	1.0	D	0.706	prob.neutral	None	None	None	None	I
D/E	0.8133	likely_pathogenic	0.7845	pathogenic	-0.681	Destabilizing	1.0	D	0.451	neutral	N	0.478877203	None	None	I
D/F	0.9779	likely_pathogenic	0.9742	pathogenic	-0.557	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	I
D/G	0.8072	likely_pathogenic	0.8033	pathogenic	-1.01	Destabilizing	1.0	D	0.727	prob.delet.	N	0.515645598	None	None	I
D/H	0.8852	likely_pathogenic	0.8775	pathogenic	-0.895	Destabilizing	1.0	D	0.693	prob.neutral	N	0.498755884	None	None	I
D/I	0.9605	likely_pathogenic	0.9481	pathogenic	0.084	Stabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
D/K	0.9642	likely_pathogenic	0.9585	pathogenic	-0.315	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	I
D/L	0.9433	likely_pathogenic	0.933	pathogenic	0.084	Stabilizing	1.0	D	0.761	deleterious	None	None	None	None	I
D/M	0.9818	likely_pathogenic	0.9795	pathogenic	0.582	Stabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	I
D/N	0.2626	likely_benign	0.2356	benign	-0.675	Destabilizing	1.0	D	0.728	prob.delet.	N	0.519271023	None	None	I
D/P	0.9745	likely_pathogenic	0.9697	pathogenic	-0.156	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	I
D/Q	0.9371	likely_pathogenic	0.9328	pathogenic	-0.581	Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	I
D/R	0.9512	likely_pathogenic	0.947	pathogenic	-0.256	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	I
D/S	0.5015	ambiguous	0.4747	ambiguous	-0.891	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	I
D/T	0.7907	likely_pathogenic	0.7952	pathogenic	-0.641	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	I
D/V	0.903	likely_pathogenic	0.8842	pathogenic	-0.156	Destabilizing	1.0	D	0.765	deleterious	N	0.49166554	None	None	I
D/W	0.9941	likely_pathogenic	0.9931	pathogenic	-0.395	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	I
D/Y	0.8415	likely_pathogenic	0.828	pathogenic	-0.324	Destabilizing	1.0	D	0.703	prob.neutral	D	0.533749853	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.