TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19937	60034;60035;60036	chr2:178592095;178592094;178592093	chr2:179456822;179456821;179456820
N2AB	18296	55111;55112;55113	chr2:178592095;178592094;178592093	chr2:179456822;179456821;179456820
N2A	17369	52330;52331;52332	chr2:178592095;178592094;178592093	chr2:179456822;179456821;179456820
N2B	10872	32839;32840;32841	chr2:178592095;178592094;178592093	chr2:179456822;179456821;179456820
Novex-1	10997	33214;33215;33216	chr2:178592095;178592094;178592093	chr2:179456822;179456821;179456820
Novex-2	11064	33415;33416;33417	chr2:178592095;178592094;178592093	chr2:179456822;179456821;179456820
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Fn3-32
• Domain position: 61
• Structural Position: 92
• Q(SASA): 0.5493
• 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
F/S	rs2050339836	None	0.014	N	0.297	0.087	0.385249989106	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	1.01626E-03	None	0	0	None	0	0	0	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
F/A	0.1967	likely_benign	0.243	benign	-2.04	Highly Destabilizing	0.004	N	0.295	neutral	None	None	None	None	N
F/C	0.1867	likely_benign	0.1968	benign	-0.678	Destabilizing	0.427	N	0.484	neutral	N	0.424261919	None	None	N
F/D	0.6169	likely_pathogenic	0.6969	pathogenic	-0.627	Destabilizing	0.085	N	0.516	neutral	None	None	None	None	N
F/E	0.5073	ambiguous	0.6046	pathogenic	-0.574	Destabilizing	0.037	N	0.431	neutral	None	None	None	None	N
F/G	0.442	ambiguous	0.4985	ambiguous	-2.342	Highly Destabilizing	0.018	N	0.33	neutral	None	None	None	None	N
F/H	0.2057	likely_benign	0.2168	benign	-0.625	Destabilizing	0.497	N	0.433	neutral	None	None	None	None	N
F/I	0.074	likely_benign	0.0814	benign	-1.149	Destabilizing	0.003	N	0.246	neutral	N	0.409137751	None	None	N
F/K	0.3493	ambiguous	0.4505	ambiguous	-0.885	Destabilizing	0.018	N	0.359	neutral	None	None	None	None	N
F/L	0.1194	likely_benign	0.1326	benign	-1.149	Destabilizing	None	N	0.074	neutral	N	0.367021769	None	None	N
F/M	0.0781	likely_benign	0.1026	benign	-0.687	Destabilizing	None	N	0.073	neutral	None	None	None	None	N
F/N	0.3144	likely_benign	0.3718	ambiguous	-0.843	Destabilizing	0.085	N	0.526	neutral	None	None	None	None	N
F/P	0.4514	ambiguous	0.5625	ambiguous	-1.437	Destabilizing	0.22	N	0.535	neutral	None	None	None	None	N
F/Q	0.2278	likely_benign	0.2798	benign	-0.956	Destabilizing	0.044	N	0.505	neutral	None	None	None	None	N
F/R	0.2747	likely_benign	0.3555	ambiguous	-0.204	Destabilizing	0.044	N	0.479	neutral	None	None	None	None	N
F/S	0.2076	likely_benign	0.2598	benign	-1.6	Destabilizing	0.014	N	0.297	neutral	N	0.401326344	None	None	N
F/T	0.1782	likely_benign	0.213	benign	-1.455	Destabilizing	0.018	N	0.275	neutral	None	None	None	None	N
F/V	0.0686	likely_benign	0.0797	benign	-1.437	Destabilizing	0.001	N	0.247	neutral	N	0.378622843	None	None	N
F/W	0.1618	likely_benign	0.139	benign	-0.59	Destabilizing	None	N	0.115	neutral	None	None	None	None	N
F/Y	0.0966	likely_benign	0.0965	benign	-0.745	Destabilizing	0.007	N	0.353	neutral	N	0.412063413	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.