TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5067	15424;15425;15426	chr2:178734725;178734724;178734723	chr2:179599452;179599451;179599450
N2AB	4750	14473;14474;14475	chr2:178734725;178734724;178734723	chr2:179599452;179599451;179599450
N2A	3823	11692;11693;11694	chr2:178734725;178734724;178734723	chr2:179599452;179599451;179599450
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-33
• Domain position: 87
• Structural Position: 172
• Q(SASA): 0.1703
• 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
T/I	rs1560840708	None	0.117	N	0.749	0.227	0.339793275041	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
T/I	rs1560840708	None	0.117	N	0.749	0.227	0.339793275041	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/I	rs1560840708	None	0.117	N	0.749	0.227	0.339793275041	gnomAD-4.0.0	1.11672E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.52739E-05	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
T/A	0.0571	likely_benign	0.0532	benign	-1.36	Destabilizing	None	N	0.161	neutral	N	0.448903	None	None	N
T/C	0.3998	ambiguous	0.3806	ambiguous	-1.115	Destabilizing	0.001	N	0.441	neutral	None	None	None	None	N
T/D	0.8546	likely_pathogenic	0.7424	pathogenic	-1.454	Destabilizing	0.149	N	0.726	prob.delet.	None	None	None	None	N
T/E	0.785	likely_pathogenic	0.6678	pathogenic	-1.25	Destabilizing	0.149	N	0.713	prob.delet.	None	None	None	None	N
T/F	0.6674	likely_pathogenic	0.6049	pathogenic	-1.217	Destabilizing	0.555	D	0.766	deleterious	None	None	None	None	N
T/G	0.2459	likely_benign	0.1897	benign	-1.761	Destabilizing	0.035	N	0.648	neutral	None	None	None	None	N
T/H	0.7324	likely_pathogenic	0.6305	pathogenic	-1.856	Destabilizing	0.824	D	0.697	prob.neutral	None	None	None	None	N
T/I	0.4151	ambiguous	0.3614	ambiguous	-0.303	Destabilizing	0.117	N	0.749	deleterious	N	0.496054513	None	None	N
T/K	0.7615	likely_pathogenic	0.6507	pathogenic	-0.474	Destabilizing	0.081	N	0.71	prob.delet.	None	None	None	None	N
T/L	0.2718	likely_benign	0.2276	benign	-0.303	Destabilizing	0.081	N	0.641	neutral	None	None	None	None	N
T/M	0.1541	likely_benign	0.1335	benign	-0.257	Destabilizing	0.555	D	0.705	prob.neutral	None	None	None	None	N
T/N	0.4358	ambiguous	0.3141	benign	-1.212	Destabilizing	0.062	N	0.689	prob.neutral	D	0.547080895	None	None	N
T/P	0.8137	likely_pathogenic	0.7232	pathogenic	-0.626	Destabilizing	0.317	N	0.764	deleterious	D	0.547251361	None	None	N
T/Q	0.6447	likely_pathogenic	0.539	ambiguous	-1.025	Destabilizing	0.38	N	0.75	deleterious	None	None	None	None	N
T/R	0.6483	likely_pathogenic	0.5408	ambiguous	-0.677	Destabilizing	0.38	N	0.762	deleterious	None	None	None	None	N
T/S	0.1255	likely_benign	0.1056	benign	-1.507	Destabilizing	0.001	N	0.145	neutral	N	0.452773827	None	None	N
T/V	0.229	likely_benign	0.2021	benign	-0.626	Destabilizing	0.081	N	0.591	neutral	None	None	None	None	N
T/W	0.9081	likely_pathogenic	0.871	pathogenic	-1.274	Destabilizing	0.935	D	0.703	prob.neutral	None	None	None	None	N
T/Y	0.7395	likely_pathogenic	0.6643	pathogenic	-0.907	Destabilizing	0.555	D	0.747	deleterious	None	None	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.