TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1147	3664;3665;3666	chr2:178781205;178781204;178781203	chr2:179645932;179645931;179645930
N2AB	1147	3664;3665;3666	chr2:178781205;178781204;178781203	chr2:179645932;179645931;179645930
N2A	1147	3664;3665;3666	chr2:178781205;178781204;178781203	chr2:179645932;179645931;179645930
N2B	1101	3526;3527;3528	chr2:178781205;178781204;178781203	chr2:179645932;179645931;179645930
Novex-1	1101	3526;3527;3528	chr2:178781205;178781204;178781203	chr2:179645932;179645931;179645930
Novex-2	1101	3526;3527;3528	chr2:178781205;178781204;178781203	chr2:179645932;179645931;179645930
Novex-3	1147	3664;3665;3666	chr2:178781205;178781204;178781203	chr2:179645932;179645931;179645930

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Ig-4
• Domain position: 66
• Structural Position: 145
• Q(SASA): 0.5032
• 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/I	None	None	0.698	N	0.446	0.446	0.456462010053	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
F/S	None	None	0.971	N	0.599	0.574	0.782198002342	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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	0.9575	likely_pathogenic	0.9496	pathogenic	-1.549	Destabilizing	0.86	D	0.517	neutral	None	None	None	None	I
F/C	0.9534	likely_pathogenic	0.94	pathogenic	-0.509	Destabilizing	0.997	D	0.631	neutral	N	0.486669245	None	None	I
F/D	0.9873	likely_pathogenic	0.9855	pathogenic	0.261	Stabilizing	0.993	D	0.709	prob.delet.	None	None	None	None	I
F/E	0.9893	likely_pathogenic	0.986	pathogenic	0.262	Stabilizing	0.978	D	0.699	prob.neutral	None	None	None	None	I
F/G	0.984	likely_pathogenic	0.9804	pathogenic	-1.803	Destabilizing	0.978	D	0.677	prob.neutral	None	None	None	None	I
F/H	0.9517	likely_pathogenic	0.9432	pathogenic	-0.311	Destabilizing	0.998	D	0.541	neutral	None	None	None	None	I
F/I	0.9195	likely_pathogenic	0.9046	pathogenic	-0.854	Destabilizing	0.698	D	0.446	neutral	N	0.458613044	None	None	I
F/K	0.9881	likely_pathogenic	0.9862	pathogenic	-0.351	Destabilizing	0.978	D	0.688	prob.neutral	None	None	None	None	I
F/L	0.9862	likely_pathogenic	0.9824	pathogenic	-0.854	Destabilizing	0.014	N	0.211	neutral	N	0.443702643	None	None	I
F/M	0.9124	likely_pathogenic	0.8959	pathogenic	-0.486	Destabilizing	0.956	D	0.509	neutral	None	None	None	None	I
F/N	0.9584	likely_pathogenic	0.9502	pathogenic	-0.152	Destabilizing	0.993	D	0.703	prob.neutral	None	None	None	None	I
F/P	0.9993	likely_pathogenic	0.9994	pathogenic	-1.07	Destabilizing	0.993	D	0.698	prob.neutral	None	None	None	None	I
F/Q	0.9822	likely_pathogenic	0.9773	pathogenic	-0.318	Destabilizing	0.993	D	0.697	prob.neutral	None	None	None	None	I
F/R	0.974	likely_pathogenic	0.9672	pathogenic	0.274	Stabilizing	0.978	D	0.709	prob.delet.	None	None	None	None	I
F/S	0.9278	likely_pathogenic	0.9104	pathogenic	-0.982	Destabilizing	0.971	D	0.599	neutral	N	0.409788674	None	None	I
F/T	0.956	likely_pathogenic	0.9464	pathogenic	-0.889	Destabilizing	0.956	D	0.541	neutral	None	None	None	None	I
F/V	0.8733	likely_pathogenic	0.8491	pathogenic	-1.07	Destabilizing	0.698	D	0.483	neutral	N	0.442779793	None	None	I
F/W	0.9021	likely_pathogenic	0.9034	pathogenic	-0.524	Destabilizing	0.998	D	0.505	neutral	None	None	None	None	I
F/Y	0.5847	likely_pathogenic	0.5596	ambiguous	-0.507	Destabilizing	0.904	D	0.487	neutral	N	0.484473168	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.