TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20198	60817;60818;60819	chr2:178591133;178591132;178591131	chr2:179455860;179455859;179455858
N2AB	18557	55894;55895;55896	chr2:178591133;178591132;178591131	chr2:179455860;179455859;179455858
N2A	17630	53113;53114;53115	chr2:178591133;178591132;178591131	chr2:179455860;179455859;179455858
N2B	11133	33622;33623;33624	chr2:178591133;178591132;178591131	chr2:179455860;179455859;179455858
Novex-1	11258	33997;33998;33999	chr2:178591133;178591132;178591131	chr2:179455860;179455859;179455858
Novex-2	11325	34198;34199;34200	chr2:178591133;178591132;178591131	chr2:179455860;179455859;179455858
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: Fn3-34
• Domain position: 28
• Structural Position: 29
• Q(SASA): 0.64
• 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/N	None	None	0.999	N	0.687	0.376	0.489728331402	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	6.07533E-05	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	0.7706	likely_pathogenic	0.831	pathogenic	-0.206	Destabilizing	0.999	D	0.644	neutral	N	0.488281271	None	None	I
D/C	0.9533	likely_pathogenic	0.9587	pathogenic	0.2	Stabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	I
D/E	0.4566	ambiguous	0.539	ambiguous	-0.288	Destabilizing	0.767	D	0.258	neutral	N	0.479380501	None	None	I
D/F	0.9225	likely_pathogenic	0.9372	pathogenic	-0.309	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	I
D/G	0.7546	likely_pathogenic	0.8076	pathogenic	-0.385	Destabilizing	0.998	D	0.667	neutral	N	0.49356119	None	None	I
D/H	0.8511	likely_pathogenic	0.8772	pathogenic	-0.247	Destabilizing	1.0	D	0.68	prob.neutral	N	0.4820403	None	None	I
D/I	0.878	likely_pathogenic	0.9039	pathogenic	0.21	Stabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	I
D/K	0.9269	likely_pathogenic	0.9443	pathogenic	0.377	Stabilizing	0.999	D	0.673	neutral	None	None	None	None	I
D/L	0.8891	likely_pathogenic	0.9063	pathogenic	0.21	Stabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	I
D/M	0.9417	likely_pathogenic	0.9585	pathogenic	0.421	Stabilizing	1.0	D	0.69	prob.neutral	None	None	None	None	I
D/N	0.3167	likely_benign	0.363	ambiguous	0.17	Stabilizing	0.999	D	0.687	prob.neutral	N	0.475252671	None	None	I
D/P	0.9957	likely_pathogenic	0.9967	pathogenic	0.094	Stabilizing	1.0	D	0.746	deleterious	None	None	None	None	I
D/Q	0.8656	likely_pathogenic	0.8999	pathogenic	0.192	Stabilizing	0.999	D	0.742	deleterious	None	None	None	None	I
D/R	0.9349	likely_pathogenic	0.9473	pathogenic	0.433	Stabilizing	0.999	D	0.717	prob.delet.	None	None	None	None	I
D/S	0.5987	likely_pathogenic	0.6708	pathogenic	0.07	Stabilizing	0.997	D	0.618	neutral	None	None	None	None	I
D/T	0.7959	likely_pathogenic	0.8461	pathogenic	0.207	Stabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	I
D/V	0.7404	likely_pathogenic	0.7894	pathogenic	0.094	Stabilizing	0.999	D	0.731	prob.delet.	N	0.49502922	None	None	I
D/W	0.9844	likely_pathogenic	0.9874	pathogenic	-0.24	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	I
D/Y	0.6397	likely_pathogenic	0.6523	pathogenic	-0.088	Destabilizing	1.0	D	0.688	prob.neutral	N	0.516113287	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.