TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6621	20086;20087;20088	chr2:178727717;178727716;178727715	chr2:179592444;179592443;179592442
N2AB	6304	19135;19136;19137	chr2:178727717;178727716;178727715	chr2:179592444;179592443;179592442
N2A	5377	16354;16355;16356	chr2:178727717;178727716;178727715	chr2:179592444;179592443;179592442
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: TTC
• RefSeq wild type template codon: AAG
• Domain: Ig-50
• Domain position: 48
• Structural Position: 122
• Q(SASA): 0.4942
• 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/L	rs760276555	-1.128	0.026	N	0.165	0.187	0.313518423057	gnomAD-2.1.1	8.04E-06	None	None	None	None	N	None	0	0	None	0	5.57E-05	None	0	None	0	8.88E-06	0
F/L	rs760276555	-1.128	0.026	N	0.165	0.187	0.313518423057	gnomAD-4.0.0	4.77693E-06	None	None	None	None	N	None	0	0	None	0	2.77393E-05	None	0	0	2.86067E-06	0	3.0259E-05

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	0.6469	likely_pathogenic	0.5645	pathogenic	-1.597	Destabilizing	0.851	D	0.531	neutral	None	None	None	None	N
F/C	0.4834	ambiguous	0.4015	ambiguous	-0.685	Destabilizing	0.999	D	0.624	neutral	N	0.500340771	None	None	N
F/D	0.8217	likely_pathogenic	0.775	pathogenic	0.652	Stabilizing	0.976	D	0.613	neutral	None	None	None	None	N
F/E	0.8309	likely_pathogenic	0.7757	pathogenic	0.698	Stabilizing	0.976	D	0.567	neutral	None	None	None	None	N
F/G	0.8189	likely_pathogenic	0.7887	pathogenic	-1.879	Destabilizing	0.919	D	0.515	neutral	None	None	None	None	N
F/H	0.5443	ambiguous	0.5198	ambiguous	-0.165	Destabilizing	0.999	D	0.593	neutral	None	None	None	None	N
F/I	0.2825	likely_benign	0.2137	benign	-0.8	Destabilizing	0.811	D	0.477	neutral	N	0.503774	None	None	N
F/K	0.8355	likely_pathogenic	0.8027	pathogenic	-0.466	Destabilizing	0.976	D	0.557	neutral	None	None	None	None	N
F/L	0.8662	likely_pathogenic	0.8196	pathogenic	-0.8	Destabilizing	0.026	N	0.165	neutral	N	0.500656337	None	None	N
F/M	0.6163	likely_pathogenic	0.5436	ambiguous	-0.599	Destabilizing	0.976	D	0.531	neutral	None	None	None	None	N
F/N	0.6466	likely_pathogenic	0.5987	pathogenic	-0.366	Destabilizing	0.976	D	0.623	neutral	None	None	None	None	N
F/P	0.9916	likely_pathogenic	0.9911	pathogenic	-1.051	Destabilizing	0.988	D	0.639	neutral	None	None	None	None	N
F/Q	0.7588	likely_pathogenic	0.7033	pathogenic	-0.417	Destabilizing	0.988	D	0.64	neutral	None	None	None	None	N
F/R	0.6979	likely_pathogenic	0.663	pathogenic	0.086	Stabilizing	0.988	D	0.631	neutral	None	None	None	None	N
F/S	0.4459	ambiguous	0.3651	ambiguous	-1.281	Destabilizing	0.251	N	0.331	neutral	N	0.467389126	None	None	N
F/T	0.5763	likely_pathogenic	0.4842	ambiguous	-1.144	Destabilizing	0.851	D	0.501	neutral	None	None	None	None	N
F/V	0.2785	likely_benign	0.2184	benign	-1.051	Destabilizing	0.811	D	0.515	neutral	N	0.498232108	None	None	N
F/W	0.643	likely_pathogenic	0.6515	pathogenic	-0.094	Destabilizing	0.999	D	0.557	neutral	None	None	None	None	N
F/Y	0.1477	likely_benign	0.1668	benign	-0.246	Destabilizing	0.946	D	0.518	neutral	N	0.480417138	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.