TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22012	66259;66260;66261	chr2:178582422;178582421;178582420	chr2:179447149;179447148;179447147
N2AB	20371	61336;61337;61338	chr2:178582422;178582421;178582420	chr2:179447149;179447148;179447147
N2A	19444	58555;58556;58557	chr2:178582422;178582421;178582420	chr2:179447149;179447148;179447147
N2B	12947	39064;39065;39066	chr2:178582422;178582421;178582420	chr2:179447149;179447148;179447147
Novex-1	13072	39439;39440;39441	chr2:178582422;178582421;178582420	chr2:179447149;179447148;179447147
Novex-2	13139	39640;39641;39642	chr2:178582422;178582421;178582420	chr2:179447149;179447148;179447147
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-47
• Domain position: 57
• Structural Position: 88
• Q(SASA): 0.4933
• 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
I/T	rs1356992317	None	0.016	N	0.174	0.237	0.37479162749	gnomAD-4.0.0	1.59313E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86121E-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	0.2297	likely_benign	0.2444	benign	-1.335	Destabilizing	0.25	N	0.307	neutral	None	None	None	None	N
I/C	0.6575	likely_pathogenic	0.6572	pathogenic	-0.806	Destabilizing	0.992	D	0.347	neutral	None	None	None	None	N
I/D	0.5613	ambiguous	0.6146	pathogenic	-0.94	Destabilizing	0.005	N	0.301	neutral	None	None	None	None	N
I/E	0.4321	ambiguous	0.493	ambiguous	-0.898	Destabilizing	0.447	N	0.389	neutral	None	None	None	None	N
I/F	0.1766	likely_benign	0.2028	benign	-0.867	Destabilizing	0.009	N	0.12	neutral	N	0.466801975	None	None	N
I/G	0.4689	ambiguous	0.4994	ambiguous	-1.633	Destabilizing	0.617	D	0.442	neutral	None	None	None	None	N
I/H	0.491	ambiguous	0.5276	ambiguous	-0.626	Destabilizing	0.992	D	0.366	neutral	None	None	None	None	N
I/K	0.3514	ambiguous	0.3985	ambiguous	-0.831	Destabilizing	0.021	N	0.303	neutral	None	None	None	None	N
I/L	0.1062	likely_benign	0.1056	benign	-0.582	Destabilizing	0.201	N	0.189	neutral	N	0.474477308	None	None	N
I/M	0.0993	likely_benign	0.1044	benign	-0.645	Destabilizing	0.896	D	0.381	neutral	N	0.494545936	None	None	N
I/N	0.2176	likely_benign	0.2458	benign	-0.888	Destabilizing	0.681	D	0.433	neutral	N	0.4662819	None	None	N
I/P	0.8711	likely_pathogenic	0.8478	pathogenic	-0.805	Destabilizing	0.92	D	0.433	neutral	None	None	None	None	N
I/Q	0.3785	ambiguous	0.418	ambiguous	-0.981	Destabilizing	0.85	D	0.431	neutral	None	None	None	None	N
I/R	0.3444	ambiguous	0.3793	ambiguous	-0.306	Destabilizing	0.739	D	0.425	neutral	None	None	None	None	N
I/S	0.2257	likely_benign	0.2424	benign	-1.413	Destabilizing	0.379	N	0.369	neutral	N	0.389474555	None	None	N
I/T	0.1849	likely_benign	0.2217	benign	-1.251	Destabilizing	0.016	N	0.174	neutral	N	0.385180669	None	None	N
I/V	0.0652	likely_benign	0.0675	benign	-0.805	Destabilizing	0.016	N	0.11	neutral	N	0.440172734	None	None	N
I/W	0.8248	likely_pathogenic	0.8451	pathogenic	-0.959	Destabilizing	0.992	D	0.397	neutral	None	None	None	None	N
I/Y	0.5321	ambiguous	0.5415	ambiguous	-0.699	Destabilizing	0.739	D	0.419	neutral	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.