TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24440	73543;73544;73545	chr2:178572814;178572813;178572812	chr2:179437541;179437540;179437539
N2AB	22799	68620;68621;68622	chr2:178572814;178572813;178572812	chr2:179437541;179437540;179437539
N2A	21872	65839;65840;65841	chr2:178572814;178572813;178572812	chr2:179437541;179437540;179437539
N2B	15375	46348;46349;46350	chr2:178572814;178572813;178572812	chr2:179437541;179437540;179437539
Novex-1	15500	46723;46724;46725	chr2:178572814;178572813;178572812	chr2:179437541;179437540;179437539
Novex-2	15567	46924;46925;46926	chr2:178572814;178572813;178572812	chr2:179437541;179437540;179437539
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-132
• Domain position: 10
• Structural Position: 16
• Q(SASA): 0.116
• 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
I/L	rs373311221	-1.038	0.006	N	0.219	0.196	0.533131753447	gnomAD-2.1.1	8.06E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
I/L	rs373311221	-1.038	0.006	N	0.219	0.196	0.533131753447	gnomAD-4.0.0	4.79049E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	6.29733E-06	0	0
I/T	rs370931683	-2.072	0.822	N	0.607	0.404	None	gnomAD-2.1.1	3.94E-05	None	None	None	None	I	None	3.72147E-04	0	None	0	0	None	0	None	4E-05	7.84E-06	0
I/T	rs370931683	-2.072	0.822	N	0.607	0.404	None	gnomAD-3.1.2	7.89E-05	None	None	None	None	I	None	2.89603E-04	0	0	0	0	None	0	0	0	0	0
I/T	rs370931683	-2.072	0.822	N	0.607	0.404	None	1000 genomes	3.99361E-04	None	None	None	None	I	None	1.5E-03	0	None	None	0	0	None	None	None	0	None
I/T	rs370931683	-2.072	0.822	N	0.607	0.404	None	gnomAD-4.0.0	1.36355E-05	None	None	None	None	I	None	2.53313E-04	0	None	0	0	None	1.56216E-05	0	0	0	3.20164E-05
I/V	rs373311221	-1.398	0.014	N	0.227	0.094	0.520854953866	gnomAD-2.1.1	8.06E-06	None	None	None	None	I	None	0	0	None	0	1.11869E-04	None	0	None	0	0	0
I/V	rs373311221	-1.398	0.014	N	0.227	0.094	0.520854953866	gnomAD-4.0.0	4.10614E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	3.47222E-04	3.59847E-06	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
I/A	0.728	likely_pathogenic	0.7559	pathogenic	-2.049	Highly Destabilizing	0.754	D	0.533	neutral	None	None	None	None	I
I/C	0.8689	likely_pathogenic	0.8861	pathogenic	-1.275	Destabilizing	0.998	D	0.573	neutral	None	None	None	None	I
I/D	0.9913	likely_pathogenic	0.9925	pathogenic	-1.689	Destabilizing	0.993	D	0.675	prob.neutral	None	None	None	None	I
I/E	0.969	likely_pathogenic	0.9713	pathogenic	-1.59	Destabilizing	0.978	D	0.671	neutral	None	None	None	None	I
I/F	0.5738	likely_pathogenic	0.6011	pathogenic	-1.252	Destabilizing	0.956	D	0.595	neutral	None	None	None	None	I
I/G	0.9587	likely_pathogenic	0.9667	pathogenic	-2.478	Highly Destabilizing	0.978	D	0.662	neutral	None	None	None	None	I
I/H	0.9641	likely_pathogenic	0.9636	pathogenic	-1.734	Destabilizing	0.998	D	0.643	neutral	None	None	None	None	I
I/K	0.9438	likely_pathogenic	0.9441	pathogenic	-1.527	Destabilizing	0.97	D	0.67	neutral	N	0.503662588	None	None	I
I/L	0.1193	likely_benign	0.1353	benign	-0.887	Destabilizing	0.006	N	0.219	neutral	N	0.490884848	None	None	I
I/M	0.2008	likely_benign	0.2153	benign	-0.712	Destabilizing	0.942	D	0.566	neutral	N	0.514511915	None	None	I
I/N	0.9097	likely_pathogenic	0.9096	pathogenic	-1.518	Destabilizing	0.993	D	0.682	prob.neutral	None	None	None	None	I
I/P	0.9871	likely_pathogenic	0.9859	pathogenic	-1.247	Destabilizing	0.993	D	0.679	prob.neutral	None	None	None	None	I
I/Q	0.9321	likely_pathogenic	0.9351	pathogenic	-1.568	Destabilizing	0.993	D	0.682	prob.neutral	None	None	None	None	I
I/R	0.9227	likely_pathogenic	0.9236	pathogenic	-1.028	Destabilizing	0.97	D	0.681	prob.neutral	N	0.514765404	None	None	I
I/S	0.8574	likely_pathogenic	0.8658	pathogenic	-2.208	Highly Destabilizing	0.978	D	0.615	neutral	None	None	None	None	I
I/T	0.7308	likely_pathogenic	0.7419	pathogenic	-1.984	Destabilizing	0.822	D	0.607	neutral	N	0.486999911	None	None	I
I/V	0.0805	likely_benign	0.0856	benign	-1.247	Destabilizing	0.014	N	0.227	neutral	N	0.384770529	None	None	I
I/W	0.9816	likely_pathogenic	0.9816	pathogenic	-1.465	Destabilizing	0.998	D	0.632	neutral	None	None	None	None	I
I/Y	0.926	likely_pathogenic	0.9269	pathogenic	-1.209	Destabilizing	0.978	D	0.627	neutral	None	None	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.