TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24348	73267;73268;73269	chr2:178573090;178573089;178573088	chr2:179437817;179437816;179437815
N2AB	22707	68344;68345;68346	chr2:178573090;178573089;178573088	chr2:179437817;179437816;179437815
N2A	21780	65563;65564;65565	chr2:178573090;178573089;178573088	chr2:179437817;179437816;179437815
N2B	15283	46072;46073;46074	chr2:178573090;178573089;178573088	chr2:179437817;179437816;179437815
Novex-1	15408	46447;46448;46449	chr2:178573090;178573089;178573088	chr2:179437817;179437816;179437815
Novex-2	15475	46648;46649;46650	chr2:178573090;178573089;178573088	chr2:179437817;179437816;179437815
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: Fn3-65
• Domain position: 26
• Structural Position: 28
• Q(SASA): 1.0104
• 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	rs1708838358	None	0.003	N	0.125	0.098	0.307016933798	gnomAD-4.0.0	1.36885E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79927E-06	0	0
I/S	rs1708837698	None	0.884	N	0.435	0.383	0.633100741311	gnomAD-4.0.0	1.59241E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85994E-06	0	0
I/V	None	None	0.001	N	0.121	0.062	0.342865806769	gnomAD-4.0.0	1.36885E-06	None	None	None	None	I	None	2.99007E-05	0	None	0	0	None	0	0	8.99637E-07	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	0.4725	ambiguous	0.4991	ambiguous	-0.471	Destabilizing	0.373	N	0.431	neutral	None	None	None	None	I
I/C	0.8142	likely_pathogenic	0.8265	pathogenic	-0.775	Destabilizing	0.996	D	0.415	neutral	None	None	None	None	I
I/D	0.9132	likely_pathogenic	0.9251	pathogenic	-0.349	Destabilizing	0.984	D	0.447	neutral	None	None	None	None	I
I/E	0.8787	likely_pathogenic	0.8939	pathogenic	-0.442	Destabilizing	0.953	D	0.433	neutral	None	None	None	None	I
I/F	0.3311	likely_benign	0.3429	ambiguous	-0.621	Destabilizing	0.884	D	0.401	neutral	N	0.492458326	None	None	I
I/G	0.8115	likely_pathogenic	0.8222	pathogenic	-0.574	Destabilizing	0.953	D	0.405	neutral	None	None	None	None	I
I/H	0.7703	likely_pathogenic	0.8001	pathogenic	0.077	Stabilizing	0.996	D	0.406	neutral	None	None	None	None	I
I/K	0.796	likely_pathogenic	0.8285	pathogenic	-0.38	Destabilizing	0.953	D	0.423	neutral	None	None	None	None	I
I/L	0.1383	likely_benign	0.129	benign	-0.321	Destabilizing	0.003	N	0.125	neutral	N	0.464972391	None	None	I
I/M	0.1805	likely_benign	0.1783	benign	-0.613	Destabilizing	0.884	D	0.464	neutral	N	0.472746512	None	None	I
I/N	0.567	likely_pathogenic	0.6177	pathogenic	-0.249	Destabilizing	0.979	D	0.437	neutral	N	0.495852658	None	None	I
I/P	0.7884	likely_pathogenic	0.7994	pathogenic	-0.343	Destabilizing	0.984	D	0.445	neutral	None	None	None	None	I
I/Q	0.7447	likely_pathogenic	0.7869	pathogenic	-0.44	Destabilizing	0.984	D	0.422	neutral	None	None	None	None	I
I/R	0.6655	likely_pathogenic	0.7203	pathogenic	0.106	Stabilizing	0.953	D	0.437	neutral	None	None	None	None	I
I/S	0.5353	ambiguous	0.5653	pathogenic	-0.605	Destabilizing	0.884	D	0.435	neutral	N	0.4731678	None	None	I
I/T	0.5385	ambiguous	0.5725	pathogenic	-0.6	Destabilizing	0.684	D	0.472	neutral	N	0.467607264	None	None	I
I/V	0.0755	likely_benign	0.0763	benign	-0.343	Destabilizing	0.001	N	0.121	neutral	N	0.466569901	None	None	I
I/W	0.9166	likely_pathogenic	0.9257	pathogenic	-0.642	Destabilizing	0.996	D	0.509	neutral	None	None	None	None	I
I/Y	0.7413	likely_pathogenic	0.7486	pathogenic	-0.41	Destabilizing	0.953	D	0.431	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.