TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27496	82711;82712;82713	chr2:178563646;178563645;178563644	chr2:179428373;179428372;179428371
N2AB	25855	77788;77789;77790	chr2:178563646;178563645;178563644	chr2:179428373;179428372;179428371
N2A	24928	75007;75008;75009	chr2:178563646;178563645;178563644	chr2:179428373;179428372;179428371
N2B	18431	55516;55517;55518	chr2:178563646;178563645;178563644	chr2:179428373;179428372;179428371
Novex-1	18556	55891;55892;55893	chr2:178563646;178563645;178563644	chr2:179428373;179428372;179428371
Novex-2	18623	56092;56093;56094	chr2:178563646;178563645;178563644	chr2:179428373;179428372;179428371
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Fn3-88
• Domain position: 28
• Structural Position: 30
• Q(SASA): 0.3351
• 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/A	None	None	0.896	N	0.671	0.397	0.418221603839	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
D/E	None	None	0.9	N	0.509	0.313	0.323615622048	gnomAD-4.0.0	6.84199E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99471E-07	0	0
D/G	rs1466312104	None	0.811	D	0.595	0.389	0.368183359018	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
D/N	rs554231442	0.061	0.06	N	0.169	0.143	0.238705975628	gnomAD-2.1.1	4.78138E-04	None	None	None	None	I	None	0	0	None	0	3.07503E-04	None	3.98667E-03	None	0	4.68E-05	0
D/N	rs554231442	0.061	0.06	N	0.169	0.143	0.238705975628	gnomAD-3.1.2	2.49872E-04	None	None	None	None	I	None	2.41E-05	6.56E-05	0	0	7.74893E-04	None	0	0	5.88E-05	5.7947E-03	0
D/N	rs554231442	0.061	0.06	N	0.169	0.143	0.238705975628	1000 genomes	9.98403E-04	None	None	None	None	I	None	0	0	None	None	0	0	None	None	None	5.1E-03	None
D/N	rs554231442	0.061	0.06	N	0.169	0.143	0.238705975628	gnomAD-4.0.0	2.85049E-04	None	None	None	None	I	None	1.33308E-05	1.66694E-05	None	0	1.33821E-04	None	0	8.2481E-04	5.84861E-05	4.04023E-03	1.60051E-04

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	0.5236	ambiguous	0.5152	ambiguous	-0.141	Destabilizing	0.896	D	0.671	neutral	N	0.495197486	None	None	I
D/C	0.8623	likely_pathogenic	0.8391	pathogenic	0.259	Stabilizing	0.999	D	0.766	deleterious	None	None	None	None	I
D/E	0.687	likely_pathogenic	0.6581	pathogenic	-0.569	Destabilizing	0.9	D	0.509	neutral	N	0.502412734	None	None	I
D/F	0.9198	likely_pathogenic	0.9123	pathogenic	-0.415	Destabilizing	0.996	D	0.752	deleterious	None	None	None	None	I
D/G	0.4678	ambiguous	0.4688	ambiguous	-0.38	Destabilizing	0.811	D	0.595	neutral	D	0.525520646	None	None	I
D/H	0.6645	likely_pathogenic	0.6364	pathogenic	-0.761	Destabilizing	0.994	D	0.697	prob.neutral	N	0.50813718	None	None	I
D/I	0.826	likely_pathogenic	0.7904	pathogenic	0.443	Stabilizing	0.988	D	0.753	deleterious	None	None	None	None	I
D/K	0.8288	likely_pathogenic	0.8278	pathogenic	0.192	Stabilizing	0.919	D	0.601	neutral	None	None	None	None	I
D/L	0.8057	likely_pathogenic	0.792	pathogenic	0.443	Stabilizing	0.988	D	0.738	prob.delet.	None	None	None	None	I
D/M	0.9114	likely_pathogenic	0.9053	pathogenic	0.85	Stabilizing	0.999	D	0.747	deleterious	None	None	None	None	I
D/N	0.1292	likely_benign	0.1155	benign	-0.026	Destabilizing	0.06	N	0.169	neutral	N	0.502570774	None	None	I
D/P	0.8853	likely_pathogenic	0.8901	pathogenic	0.273	Stabilizing	0.996	D	0.685	prob.neutral	None	None	None	None	I
D/Q	0.8187	likely_pathogenic	0.8098	pathogenic	0.022	Stabilizing	0.988	D	0.639	neutral	None	None	None	None	I
D/R	0.8173	likely_pathogenic	0.8085	pathogenic	0.083	Stabilizing	0.976	D	0.723	prob.delet.	None	None	None	None	I
D/S	0.2338	likely_benign	0.2355	benign	-0.152	Destabilizing	0.851	D	0.579	neutral	None	None	None	None	I
D/T	0.4121	ambiguous	0.3945	ambiguous	0.034	Stabilizing	0.919	D	0.606	neutral	None	None	None	None	I
D/V	0.6925	likely_pathogenic	0.6538	pathogenic	0.273	Stabilizing	0.984	D	0.747	deleterious	N	0.517669833	None	None	I
D/W	0.9792	likely_pathogenic	0.9782	pathogenic	-0.44	Destabilizing	0.999	D	0.74	deleterious	None	None	None	None	I
D/Y	0.5733	likely_pathogenic	0.5517	ambiguous	-0.213	Destabilizing	0.998	D	0.754	deleterious	D	0.548397841	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.