TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31721	95386;95387;95388	chr2:178546075;178546074;178546073	chr2:179410802;179410801;179410800
N2AB	30080	90463;90464;90465	chr2:178546075;178546074;178546073	chr2:179410802;179410801;179410800
N2A	29153	87682;87683;87684	chr2:178546075;178546074;178546073	chr2:179410802;179410801;179410800
N2B	22656	68191;68192;68193	chr2:178546075;178546074;178546073	chr2:179410802;179410801;179410800
Novex-1	22781	68566;68567;68568	chr2:178546075;178546074;178546073	chr2:179410802;179410801;179410800
Novex-2	22848	68767;68768;68769	chr2:178546075;178546074;178546073	chr2:179410802;179410801;179410800
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-119
• Domain position: 14
• Structural Position: 16
• Q(SASA): 0.303
• 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
T/I	None	None	1.0	N	0.755	0.527	0.515715180578	gnomAD-4.0.0	6.84617E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99956E-07	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
T/A	0.3566	ambiguous	0.3621	ambiguous	-0.685	Destabilizing	0.999	D	0.508	neutral	N	0.491251147	None	None	N
T/C	0.7795	likely_pathogenic	0.7616	pathogenic	-0.587	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	N
T/D	0.6889	likely_pathogenic	0.6514	pathogenic	-1.065	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
T/E	0.7967	likely_pathogenic	0.793	pathogenic	-1.056	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
T/F	0.6088	likely_pathogenic	0.612	pathogenic	-0.721	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
T/G	0.4032	ambiguous	0.3837	ambiguous	-0.95	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
T/H	0.5953	likely_pathogenic	0.571	pathogenic	-1.291	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	N
T/I	0.7582	likely_pathogenic	0.781	pathogenic	-0.065	Destabilizing	1.0	D	0.755	deleterious	N	0.519839562	None	None	N
T/K	0.7091	likely_pathogenic	0.7245	pathogenic	-0.911	Destabilizing	1.0	D	0.772	deleterious	N	0.495441429	None	None	N
T/L	0.3029	likely_benign	0.3274	benign	-0.065	Destabilizing	0.999	D	0.671	neutral	None	None	None	None	N
T/M	0.2236	likely_benign	0.2609	benign	0.278	Stabilizing	1.0	D	0.696	prob.neutral	None	None	None	None	N
T/N	0.2114	likely_benign	0.2009	benign	-0.977	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
T/P	0.7978	likely_pathogenic	0.7862	pathogenic	-0.24	Destabilizing	1.0	D	0.735	prob.delet.	D	0.524447917	None	None	N
T/Q	0.5854	likely_pathogenic	0.5897	pathogenic	-1.2	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
T/R	0.65	likely_pathogenic	0.6577	pathogenic	-0.619	Destabilizing	1.0	D	0.739	prob.delet.	N	0.480615631	None	None	N
T/S	0.1436	likely_benign	0.1346	benign	-1.116	Destabilizing	0.999	D	0.532	neutral	N	0.455451617	None	None	N
T/V	0.6271	likely_pathogenic	0.6509	pathogenic	-0.24	Destabilizing	0.999	D	0.604	neutral	None	None	None	None	N
T/W	0.8914	likely_pathogenic	0.8881	pathogenic	-0.708	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
T/Y	0.6676	likely_pathogenic	0.6548	pathogenic	-0.448	Destabilizing	1.0	D	0.744	deleterious	None	None	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.