TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21275	64048;64049;64050	chr2:178587388;178587387;178587386	chr2:179452115;179452114;179452113
N2AB	19634	59125;59126;59127	chr2:178587388;178587387;178587386	chr2:179452115;179452114;179452113
N2A	18707	56344;56345;56346	chr2:178587388;178587387;178587386	chr2:179452115;179452114;179452113
N2B	12210	36853;36854;36855	chr2:178587388;178587387;178587386	chr2:179452115;179452114;179452113
Novex-1	12335	37228;37229;37230	chr2:178587388;178587387;178587386	chr2:179452115;179452114;179452113
Novex-2	12402	37429;37430;37431	chr2:178587388;178587387;178587386	chr2:179452115;179452114;179452113
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-42
• Domain position: 10
• Structural Position: 12
• Q(SASA): 0.3359
• 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
V/L	rs2049255613	None	0.027	N	0.497	0.103	0.260735089382	gnomAD-4.0.0	1.6062E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.44001E-05	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
V/A	0.2404	likely_benign	0.3196	benign	-1.511	Destabilizing	None	N	0.187	neutral	N	0.486793245	None	None	N
V/C	0.6836	likely_pathogenic	0.7624	pathogenic	-1.219	Destabilizing	0.824	D	0.625	neutral	None	None	None	None	N
V/D	0.8943	likely_pathogenic	0.9285	pathogenic	-1.017	Destabilizing	0.317	N	0.695	prob.neutral	D	0.524323013	None	None	N
V/E	0.8588	likely_pathogenic	0.8954	pathogenic	-0.919	Destabilizing	0.149	N	0.619	neutral	None	None	None	None	N
V/F	0.2867	likely_benign	0.3558	ambiguous	-0.921	Destabilizing	0.484	N	0.623	neutral	N	0.475562748	None	None	N
V/G	0.4497	ambiguous	0.5624	ambiguous	-1.927	Destabilizing	0.062	N	0.611	neutral	N	0.502736038	None	None	N
V/H	0.9179	likely_pathogenic	0.9456	pathogenic	-1.354	Destabilizing	0.935	D	0.691	prob.neutral	None	None	None	None	N
V/I	0.0839	likely_benign	0.0883	benign	-0.433	Destabilizing	0.052	N	0.575	neutral	N	0.505765795	None	None	N
V/K	0.903	likely_pathogenic	0.9275	pathogenic	-1.229	Destabilizing	0.149	N	0.624	neutral	None	None	None	None	N
V/L	0.2809	likely_benign	0.3374	benign	-0.433	Destabilizing	0.027	N	0.497	neutral	N	0.51590543	None	None	N
V/M	0.2695	likely_benign	0.3354	benign	-0.498	Destabilizing	0.555	D	0.548	neutral	None	None	None	None	N
V/N	0.7661	likely_pathogenic	0.8401	pathogenic	-1.235	Destabilizing	0.38	N	0.693	prob.neutral	None	None	None	None	N
V/P	0.5	ambiguous	0.5823	pathogenic	-0.758	Destabilizing	0.38	N	0.646	neutral	None	None	None	None	N
V/Q	0.8578	likely_pathogenic	0.8951	pathogenic	-1.213	Destabilizing	0.555	D	0.65	neutral	None	None	None	None	N
V/R	0.8698	likely_pathogenic	0.9021	pathogenic	-0.907	Destabilizing	0.38	N	0.693	prob.neutral	None	None	None	None	N
V/S	0.5213	ambiguous	0.6306	pathogenic	-1.907	Destabilizing	0.081	N	0.551	neutral	None	None	None	None	N
V/T	0.3965	ambiguous	0.4847	ambiguous	-1.66	Destabilizing	0.001	N	0.298	neutral	None	None	None	None	N
V/W	0.9195	likely_pathogenic	0.9469	pathogenic	-1.155	Destabilizing	0.935	D	0.711	prob.delet.	None	None	None	None	N
V/Y	0.7248	likely_pathogenic	0.805	pathogenic	-0.827	Destabilizing	0.555	D	0.628	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.