TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32733	98422;98423;98424	chr2:178539868;178539867;178539866	chr2:179404595;179404594;179404593
N2AB	31092	93499;93500;93501	chr2:178539868;178539867;178539866	chr2:179404595;179404594;179404593
N2A	30165	90718;90719;90720	chr2:178539868;178539867;178539866	chr2:179404595;179404594;179404593
N2B	23668	71227;71228;71229	chr2:178539868;178539867;178539866	chr2:179404595;179404594;179404593
Novex-1	23793	71602;71603;71604	chr2:178539868;178539867;178539866	chr2:179404595;179404594;179404593
Novex-2	23860	71803;71804;71805	chr2:178539868;178539867;178539866	chr2:179404595;179404594;179404593
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: Ig-155
• Domain position: 26
• Structural Position: 43
• Q(SASA): 0.4277
• 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
F/S	None	None	None	N	0.191	0.239	0.54173910141	gnomAD-4.0.0	2.40065E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.62501E-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
F/A	0.1839	likely_benign	0.2015	benign	-1.321	Destabilizing	0.004	N	0.351	neutral	None	None	None	None	I
F/C	0.193	likely_benign	0.2057	benign	-0.428	Destabilizing	0.427	N	0.429	neutral	N	0.492615644	None	None	I
F/D	0.5221	ambiguous	0.5273	ambiguous	0.372	Stabilizing	0.044	N	0.47	neutral	None	None	None	None	I
F/E	0.5436	ambiguous	0.5441	ambiguous	0.376	Stabilizing	0.044	N	0.467	neutral	None	None	None	None	I
F/G	0.4974	ambiguous	0.5119	ambiguous	-1.558	Destabilizing	0.009	N	0.429	neutral	None	None	None	None	I
F/H	0.3494	ambiguous	0.3533	ambiguous	-0.06	Destabilizing	0.138	N	0.341	neutral	None	None	None	None	I
F/I	0.076	likely_benign	0.0878	benign	-0.677	Destabilizing	None	N	0.169	neutral	N	0.390451281	None	None	I
F/K	0.4722	ambiguous	0.4816	ambiguous	-0.412	Destabilizing	0.044	N	0.464	neutral	None	None	None	None	I
F/L	0.428	ambiguous	0.4426	ambiguous	-0.677	Destabilizing	None	N	0.171	neutral	N	0.388680413	None	None	I
F/M	0.1968	likely_benign	0.2101	benign	-0.52	Destabilizing	0.002	N	0.233	neutral	None	None	None	None	I
F/N	0.235	likely_benign	0.2495	benign	-0.334	Destabilizing	0.044	N	0.497	neutral	None	None	None	None	I
F/P	0.5154	ambiguous	0.509	ambiguous	-0.875	Destabilizing	0.085	N	0.471	neutral	None	None	None	None	I
F/Q	0.4206	ambiguous	0.4313	ambiguous	-0.406	Destabilizing	0.085	N	0.473	neutral	None	None	None	None	I
F/R	0.4144	ambiguous	0.4369	ambiguous	0.118	Stabilizing	0.044	N	0.483	neutral	None	None	None	None	I
F/S	0.1501	likely_benign	0.1626	benign	-1.037	Destabilizing	None	N	0.191	neutral	N	0.424254424	None	None	I
F/T	0.1768	likely_benign	0.1991	benign	-0.943	Destabilizing	0.009	N	0.411	neutral	None	None	None	None	I
F/V	0.0806	likely_benign	0.0908	benign	-0.875	Destabilizing	None	N	0.305	neutral	N	0.415346939	None	None	I
F/W	0.4679	ambiguous	0.4607	ambiguous	-0.296	Destabilizing	0.245	N	0.279	neutral	None	None	None	None	I
F/Y	0.1194	likely_benign	0.1275	benign	-0.36	Destabilizing	None	N	0.165	neutral	N	0.492442286	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.