TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2843	8752;8753;8754	chr2:178770174;178770173;178770172	chr2:179634901;179634900;179634899
N2AB	2843	8752;8753;8754	chr2:178770174;178770173;178770172	chr2:179634901;179634900;179634899
N2A	2843	8752;8753;8754	chr2:178770174;178770173;178770172	chr2:179634901;179634900;179634899
N2B	2797	8614;8615;8616	chr2:178770174;178770173;178770172	chr2:179634901;179634900;179634899
Novex-1	2797	8614;8615;8616	chr2:178770174;178770173;178770172	chr2:179634901;179634900;179634899
Novex-2	2797	8614;8615;8616	chr2:178770174;178770173;178770172	chr2:179634901;179634900;179634899
Novex-3	2843	8752;8753;8754	chr2:178770174;178770173;178770172	chr2:179634901;179634900;179634899

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-18
• Domain position: 49
• Structural Position: 125
• Q(SASA): 0.2579
• 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/G	None	None	0.379	N	0.453	0.366	0.796139353377	gnomAD-4.0.0	1.59046E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85649E-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	0.3533	ambiguous	0.3339	benign	-1.252	Destabilizing	0.201	N	0.28	neutral	N	0.505662597	None	None	N
V/C	0.8313	likely_pathogenic	0.835	pathogenic	-0.686	Destabilizing	0.992	D	0.406	neutral	None	None	None	None	N
V/D	0.7069	likely_pathogenic	0.6541	pathogenic	-1.11	Destabilizing	0.81	D	0.484	neutral	D	0.536287553	None	None	N
V/E	0.5656	likely_pathogenic	0.5106	ambiguous	-1.173	Destabilizing	0.85	D	0.454	neutral	None	None	None	None	N
V/F	0.2142	likely_benign	0.2007	benign	-1.124	Destabilizing	0.81	D	0.418	neutral	N	0.507773072	None	None	N
V/G	0.4596	ambiguous	0.4169	ambiguous	-1.498	Destabilizing	0.379	N	0.453	neutral	N	0.500550004	None	None	N
V/H	0.7126	likely_pathogenic	0.6902	pathogenic	-1.06	Destabilizing	0.992	D	0.457	neutral	None	None	None	None	N
V/I	0.0805	likely_benign	0.0861	benign	-0.7	Destabilizing	0.002	N	0.105	neutral	N	0.490476701	None	None	N
V/K	0.6744	likely_pathogenic	0.6152	pathogenic	-1.087	Destabilizing	0.617	D	0.444	neutral	None	None	None	None	N
V/L	0.2132	likely_benign	0.2101	benign	-0.7	Destabilizing	0.002	N	0.08	neutral	N	0.475035349	None	None	N
V/M	0.1974	likely_benign	0.2168	benign	-0.43	Destabilizing	0.127	N	0.202	neutral	None	None	None	None	N
V/N	0.5213	ambiguous	0.5116	ambiguous	-0.705	Destabilizing	0.85	D	0.493	neutral	None	None	None	None	N
V/P	0.9655	likely_pathogenic	0.937	pathogenic	-0.849	Destabilizing	0.92	D	0.469	neutral	None	None	None	None	N
V/Q	0.5035	ambiguous	0.4766	ambiguous	-0.962	Destabilizing	0.92	D	0.479	neutral	None	None	None	None	N
V/R	0.6274	likely_pathogenic	0.5504	ambiguous	-0.479	Destabilizing	0.85	D	0.495	neutral	None	None	None	None	N
V/S	0.3675	ambiguous	0.366	ambiguous	-1.13	Destabilizing	0.021	N	0.293	neutral	None	None	None	None	N
V/T	0.3257	likely_benign	0.3415	ambiguous	-1.099	Destabilizing	0.447	N	0.285	neutral	None	None	None	None	N
V/W	0.887	likely_pathogenic	0.8589	pathogenic	-1.245	Destabilizing	0.992	D	0.493	neutral	None	None	None	None	N
V/Y	0.6391	likely_pathogenic	0.6363	pathogenic	-0.996	Destabilizing	0.92	D	0.431	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.