TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3246	9961;9962;9963	chr2:178764779;178764778;178764777	chr2:179629506;179629505;179629504
N2AB	3246	9961;9962;9963	chr2:178764779;178764778;178764777	chr2:179629506;179629505;179629504
N2A	3246	9961;9962;9963	chr2:178764779;178764778;178764777	chr2:179629506;179629505;179629504
N2B	3200	9823;9824;9825	chr2:178764779;178764778;178764777	chr2:179629506;179629505;179629504
Novex-1	3200	9823;9824;9825	chr2:178764779;178764778;178764777	chr2:179629506;179629505;179629504
Novex-2	3200	9823;9824;9825	chr2:178764779;178764778;178764777	chr2:179629506;179629505;179629504
Novex-3	3246	9961;9962;9963	chr2:178764779;178764778;178764777	chr2:179629506;179629505;179629504

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAG
• RefSeq wild type template codon: GTC
• Domain: Ig-23
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.5417
• 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
Q/H	None	None	0.966	D	0.353	0.264	0.331876078066	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	6.33473E-05	0	None	0	0	None	0	0	0	0	0
Q/L	None	None	0.801	N	0.381	0.495	0.652016397996	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
Q/R	None	None	0.801	N	0.346	0.249	0.208816687407	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
Q/A	0.23	likely_benign	0.3028	benign	-0.281	Destabilizing	0.688	D	0.339	neutral	None	None	None	None	I
Q/C	0.6277	likely_pathogenic	0.8021	pathogenic	-0.006	Destabilizing	0.998	D	0.394	neutral	None	None	None	None	I
Q/D	0.396	ambiguous	0.5853	pathogenic	0.028	Stabilizing	0.525	D	0.347	neutral	None	None	None	None	I
Q/E	0.0861	likely_benign	0.1021	benign	0.045	Stabilizing	0.002	N	0.099	neutral	N	0.459304165	None	None	I
Q/F	0.662	likely_pathogenic	0.7999	pathogenic	-0.339	Destabilizing	0.991	D	0.378	neutral	None	None	None	None	I
Q/G	0.297	likely_benign	0.4333	ambiguous	-0.512	Destabilizing	0.915	D	0.386	neutral	None	None	None	None	I
Q/H	0.205	likely_benign	0.3296	benign	-0.204	Destabilizing	0.966	D	0.353	neutral	D	0.543123534	None	None	I
Q/I	0.3697	ambiguous	0.4804	ambiguous	0.254	Stabilizing	0.974	D	0.382	neutral	None	None	None	None	I
Q/K	0.0955	likely_benign	0.1263	benign	-0.037	Destabilizing	0.454	N	0.377	neutral	N	0.495319605	None	None	I
Q/L	0.1252	likely_benign	0.1694	benign	0.254	Stabilizing	0.801	D	0.381	neutral	N	0.506786063	None	None	I
Q/M	0.3751	ambiguous	0.454	ambiguous	0.255	Stabilizing	0.991	D	0.354	neutral	None	None	None	None	I
Q/N	0.3059	likely_benign	0.4295	ambiguous	-0.464	Destabilizing	0.842	D	0.309	neutral	None	None	None	None	I
Q/P	0.181	likely_benign	0.3168	benign	0.105	Stabilizing	0.891	D	0.373	neutral	D	0.543123534	None	None	I
Q/R	0.1139	likely_benign	0.1543	benign	0.148	Stabilizing	0.801	D	0.346	neutral	N	0.498705242	None	None	I
Q/S	0.2498	likely_benign	0.3418	ambiguous	-0.472	Destabilizing	0.688	D	0.341	neutral	None	None	None	None	I
Q/T	0.2229	likely_benign	0.2948	benign	-0.288	Destabilizing	0.842	D	0.331	neutral	None	None	None	None	I
Q/V	0.2613	likely_benign	0.3355	benign	0.105	Stabilizing	0.915	D	0.396	neutral	None	None	None	None	I
Q/W	0.5449	ambiguous	0.7602	pathogenic	-0.318	Destabilizing	0.998	D	0.407	neutral	None	None	None	None	I
Q/Y	0.4533	ambiguous	0.6327	pathogenic	-0.063	Destabilizing	0.991	D	0.356	neutral	None	None	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.