TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17457	52594;52595;52596	chr2:178608642;178608641;178608640	chr2:179473369;179473368;179473367
N2AB	15816	47671;47672;47673	chr2:178608642;178608641;178608640	chr2:179473369;179473368;179473367
N2A	14889	44890;44891;44892	chr2:178608642;178608641;178608640	chr2:179473369;179473368;179473367
N2B	8392	25399;25400;25401	chr2:178608642;178608641;178608640	chr2:179473369;179473368;179473367
Novex-1	8517	25774;25775;25776	chr2:178608642;178608641;178608640	chr2:179473369;179473368;179473367
Novex-2	8584	25975;25976;25977	chr2:178608642;178608641;178608640	chr2:179473369;179473368;179473367
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGT
• RefSeq wild type template codon: ACA
• Domain: Fn3-14
• Domain position: 89
• Structural Position: 121
• Q(SASA): 0.0883
• 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
C/Y	rs368055091	None	0.999	D	0.897	0.4	0.663445045466	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-05	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
C/A	0.2938	likely_benign	0.3449	ambiguous	-1.705	Destabilizing	0.995	D	0.733	deleterious	None	None	None	None	N
C/D	0.8931	likely_pathogenic	0.9234	pathogenic	-0.524	Destabilizing	0.999	D	0.874	deleterious	None	None	None	None	N
C/E	0.906	likely_pathogenic	0.9321	pathogenic	-0.352	Destabilizing	0.999	D	0.891	deleterious	None	None	None	None	N
C/F	0.4905	ambiguous	0.5224	ambiguous	-0.962	Destabilizing	0.999	D	0.876	deleterious	N	0.482571549	None	None	N
C/G	0.3519	ambiguous	0.375	ambiguous	-2.061	Highly Destabilizing	0.999	D	0.857	deleterious	N	0.461903161	None	None	N
C/H	0.791	likely_pathogenic	0.8236	pathogenic	-2.082	Highly Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
C/I	0.4858	ambiguous	0.5313	ambiguous	-0.763	Destabilizing	0.999	D	0.797	deleterious	None	None	None	None	N
C/K	0.933	likely_pathogenic	0.9462	pathogenic	-0.949	Destabilizing	0.999	D	0.867	deleterious	None	None	None	None	N
C/L	0.4752	ambiguous	0.497	ambiguous	-0.763	Destabilizing	0.998	D	0.723	deleterious	None	None	None	None	N
C/M	0.618	likely_pathogenic	0.6561	pathogenic	0.202	Stabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
C/N	0.708	likely_pathogenic	0.743	pathogenic	-1.223	Destabilizing	0.999	D	0.893	deleterious	None	None	None	None	N
C/P	0.9905	likely_pathogenic	0.9922	pathogenic	-1.051	Destabilizing	0.999	D	0.888	deleterious	None	None	None	None	N
C/Q	0.7926	likely_pathogenic	0.8217	pathogenic	-0.927	Destabilizing	1.0	D	0.915	deleterious	None	None	None	None	N
C/R	0.7435	likely_pathogenic	0.7671	pathogenic	-1.076	Destabilizing	0.999	D	0.902	deleterious	N	0.49353279	None	None	N
C/S	0.3032	likely_benign	0.3395	benign	-1.722	Destabilizing	0.999	D	0.747	deleterious	N	0.393077794	None	None	N
C/T	0.4073	ambiguous	0.4481	ambiguous	-1.347	Destabilizing	0.999	D	0.758	deleterious	None	None	None	None	N
C/V	0.3489	ambiguous	0.3831	ambiguous	-1.051	Destabilizing	0.998	D	0.704	prob.delet.	None	None	None	None	N
C/W	0.8546	likely_pathogenic	0.8732	pathogenic	-1.089	Destabilizing	1.0	D	0.859	deleterious	N	0.483078528	None	None	N
C/Y	0.6729	likely_pathogenic	0.702	pathogenic	-1.016	Destabilizing	0.999	D	0.897	deleterious	D	0.524202414	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.