TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20879	62860;62861;62862	chr2:178589090;178589089;178589088	chr2:179453817;179453816;179453815
N2AB	19238	57937;57938;57939	chr2:178589090;178589089;178589088	chr2:179453817;179453816;179453815
N2A	18311	55156;55157;55158	chr2:178589090;178589089;178589088	chr2:179453817;179453816;179453815
N2B	11814	35665;35666;35667	chr2:178589090;178589089;178589088	chr2:179453817;179453816;179453815
Novex-1	11939	36040;36041;36042	chr2:178589090;178589089;178589088	chr2:179453817;179453816;179453815
Novex-2	12006	36241;36242;36243	chr2:178589090;178589089;178589088	chr2:179453817;179453816;179453815
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: Fn3-39
• Domain position: 16
• Structural Position: 18
• Q(SASA): 0.4286
• 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
D/N	None	None	1.0	N	0.595	0.37	0.24896430686	gnomAD-4.0.0	6.85819E-07	None	None	None	None	N	None	2.98882E-05	0	None	0	0	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
D/A	0.6804	likely_pathogenic	0.606	pathogenic	-0.479	Destabilizing	1.0	D	0.795	deleterious	N	0.474789053	None	None	N
D/C	0.9275	likely_pathogenic	0.9078	pathogenic	0.164	Stabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
D/E	0.3609	ambiguous	0.3053	benign	-0.485	Destabilizing	1.0	D	0.429	neutral	N	0.509688747	None	None	N
D/F	0.9195	likely_pathogenic	0.8875	pathogenic	-0.67	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
D/G	0.5872	likely_pathogenic	0.5088	ambiguous	-0.675	Destabilizing	1.0	D	0.745	deleterious	N	0.469179965	None	None	N
D/H	0.7892	likely_pathogenic	0.7482	pathogenic	-0.82	Destabilizing	1.0	D	0.742	deleterious	D	0.524484841	None	None	N
D/I	0.8724	likely_pathogenic	0.8316	pathogenic	-0.004	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
D/K	0.8875	likely_pathogenic	0.8584	pathogenic	0.255	Stabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
D/L	0.8312	likely_pathogenic	0.7895	pathogenic	-0.004	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
D/M	0.9199	likely_pathogenic	0.8938	pathogenic	0.418	Stabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
D/N	0.2685	likely_benign	0.2336	benign	0.029	Stabilizing	1.0	D	0.595	neutral	N	0.478248332	None	None	N
D/P	0.9812	likely_pathogenic	0.9723	pathogenic	-0.141	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
D/Q	0.7842	likely_pathogenic	0.7352	pathogenic	0.021	Stabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
D/R	0.8924	likely_pathogenic	0.8617	pathogenic	0.205	Stabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
D/S	0.3778	ambiguous	0.3267	benign	-0.092	Destabilizing	1.0	D	0.684	prob.neutral	None	None	None	None	N
D/T	0.5941	likely_pathogenic	0.5298	ambiguous	0.061	Stabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
D/V	0.7406	likely_pathogenic	0.6827	pathogenic	-0.141	Destabilizing	1.0	D	0.797	deleterious	N	0.495615559	None	None	N
D/W	0.981	likely_pathogenic	0.9739	pathogenic	-0.582	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
D/Y	0.7083	likely_pathogenic	0.6479	pathogenic	-0.439	Destabilizing	1.0	D	0.789	deleterious	N	0.506718375	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.