TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21013	63262;63263;63264	chr2:178588688;178588687;178588686	chr2:179453415;179453414;179453413
N2AB	19372	58339;58340;58341	chr2:178588688;178588687;178588686	chr2:179453415;179453414;179453413
N2A	18445	55558;55559;55560	chr2:178588688;178588687;178588686	chr2:179453415;179453414;179453413
N2B	11948	36067;36068;36069	chr2:178588688;178588687;178588686	chr2:179453415;179453414;179453413
Novex-1	12073	36442;36443;36444	chr2:178588688;178588687;178588686	chr2:179453415;179453414;179453413
Novex-2	12140	36643;36644;36645	chr2:178588688;178588687;178588686	chr2:179453415;179453414;179453413
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Fn3-40
• Domain position: 51
• Structural Position: 68
• Q(SASA): 0.3045
• 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/I	rs1559561777	None	0.987	N	0.5	0.229	0.353761421236	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
V/I	rs1559561777	None	0.987	N	0.5	0.229	0.353761421236	gnomAD-4.0.0	1.59243E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86041E-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
V/A	0.3255	likely_benign	0.2819	benign	-1.507	Destabilizing	0.973	D	0.492	neutral	N	0.499202395	None	None	N
V/C	0.6964	likely_pathogenic	0.6751	pathogenic	-0.903	Destabilizing	0.269	N	0.383	neutral	None	None	None	None	N
V/D	0.9732	likely_pathogenic	0.9645	pathogenic	-1.539	Destabilizing	0.999	D	0.785	deleterious	N	0.513528777	None	None	N
V/E	0.9246	likely_pathogenic	0.9121	pathogenic	-1.523	Destabilizing	1.0	D	0.734	prob.delet.	None	None	None	None	N
V/F	0.5853	likely_pathogenic	0.5867	pathogenic	-1.162	Destabilizing	0.999	D	0.719	prob.delet.	N	0.479064559	None	None	N
V/G	0.7098	likely_pathogenic	0.6424	pathogenic	-1.837	Destabilizing	0.998	D	0.724	prob.delet.	N	0.49880511	None	None	N
V/H	0.9662	likely_pathogenic	0.9566	pathogenic	-1.452	Destabilizing	1.0	D	0.758	deleterious	None	None	None	None	N
V/I	0.1012	likely_benign	0.1045	benign	-0.692	Destabilizing	0.987	D	0.5	neutral	N	0.470495641	None	None	N
V/K	0.966	likely_pathogenic	0.9538	pathogenic	-1.417	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
V/L	0.443	ambiguous	0.4232	ambiguous	-0.692	Destabilizing	0.973	D	0.505	neutral	N	0.502741345	None	None	N
V/M	0.3597	ambiguous	0.3638	ambiguous	-0.486	Destabilizing	1.0	D	0.637	neutral	None	None	None	None	N
V/N	0.8831	likely_pathogenic	0.8511	pathogenic	-1.197	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
V/P	0.9757	likely_pathogenic	0.9644	pathogenic	-0.93	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
V/Q	0.9001	likely_pathogenic	0.8765	pathogenic	-1.333	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
V/R	0.9437	likely_pathogenic	0.9271	pathogenic	-0.901	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
V/S	0.6271	likely_pathogenic	0.5568	ambiguous	-1.65	Destabilizing	0.999	D	0.665	neutral	None	None	None	None	N
V/T	0.4918	ambiguous	0.4384	ambiguous	-1.525	Destabilizing	0.996	D	0.541	neutral	None	None	None	None	N
V/W	0.9853	likely_pathogenic	0.9849	pathogenic	-1.413	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
V/Y	0.9278	likely_pathogenic	0.9179	pathogenic	-1.116	Destabilizing	1.0	D	0.724	prob.delet.	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.