TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5780	17563;17564;17565	chr2:178731428;178731427;178731426	chr2:179596155;179596154;179596153
N2AB	5463	16612;16613;16614	chr2:178731428;178731427;178731426	chr2:179596155;179596154;179596153
N2A	4536	13831;13832;13833	chr2:178731428;178731427;178731426	chr2:179596155;179596154;179596153
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Ig-41
• Domain position: 51
• Structural Position: 127
• Q(SASA): 0.3471
• 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	rs201482215	-1.012	0.998	N	0.783	0.459	None	gnomAD-2.1.1	1.46323E-04	None	None	None	None	N	None	0	0	None	0	0	None	0	None	8.79297E-04	1.24916E-04	4.20875E-04
F/S	rs201482215	-1.012	0.998	N	0.783	0.459	None	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	0	0	0	0	0	None	2.8238E-04	0	1.47E-05	0	0
F/S	rs201482215	-1.012	0.998	N	0.783	0.459	None	gnomAD-4.0.0	5.82521E-05	None	None	None	None	N	None	0	0	None	0	0	None	1.03083E-03	0	1.10189E-05	0	2.40184E-04

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	0.8712	likely_pathogenic	0.8489	pathogenic	-2.076	Highly Destabilizing	0.996	D	0.743	deleterious	None	None	None	None	N
F/C	0.7692	likely_pathogenic	0.7382	pathogenic	-1.046	Destabilizing	1.0	D	0.802	deleterious	N	0.510153367	None	None	N
F/D	0.9731	likely_pathogenic	0.9637	pathogenic	-0.603	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
F/E	0.9675	likely_pathogenic	0.9591	pathogenic	-0.54	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
F/G	0.9572	likely_pathogenic	0.9488	pathogenic	-2.397	Highly Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	N
F/H	0.8429	likely_pathogenic	0.8074	pathogenic	-0.743	Destabilizing	0.999	D	0.749	deleterious	None	None	None	None	N
F/I	0.5446	ambiguous	0.5272	ambiguous	-1.134	Destabilizing	0.998	D	0.723	prob.delet.	N	0.486769193	None	None	N
F/K	0.9686	likely_pathogenic	0.9621	pathogenic	-1.085	Destabilizing	0.999	D	0.805	deleterious	None	None	None	None	N
F/L	0.9447	likely_pathogenic	0.9425	pathogenic	-1.134	Destabilizing	0.989	D	0.649	neutral	N	0.521802401	None	None	N
F/M	0.7391	likely_pathogenic	0.7259	pathogenic	-0.822	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
F/N	0.9097	likely_pathogenic	0.8913	pathogenic	-1.071	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
F/P	0.9983	likely_pathogenic	0.9978	pathogenic	-1.439	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
F/Q	0.9465	likely_pathogenic	0.9366	pathogenic	-1.162	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
F/R	0.9298	likely_pathogenic	0.9144	pathogenic	-0.423	Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	N
F/S	0.775	likely_pathogenic	0.7398	pathogenic	-1.884	Destabilizing	0.998	D	0.783	deleterious	N	0.521282326	None	None	N
F/T	0.8006	likely_pathogenic	0.7648	pathogenic	-1.726	Destabilizing	0.999	D	0.797	deleterious	None	None	None	None	N
F/V	0.4991	ambiguous	0.4848	ambiguous	-1.439	Destabilizing	0.989	D	0.72	prob.delet.	N	0.517548587	None	None	N
F/W	0.6309	likely_pathogenic	0.595	pathogenic	-0.459	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
F/Y	0.2458	likely_benign	0.221	benign	-0.619	Destabilizing	0.333	N	0.304	neutral	N	0.479531704	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.