TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6631	20116;20117;20118	chr2:178727687;178727686;178727685	chr2:179592414;179592413;179592412
N2AB	6314	19165;19166;19167	chr2:178727687;178727686;178727685	chr2:179592414;179592413;179592412
N2A	5387	16384;16385;16386	chr2:178727687;178727686;178727685	chr2:179592414;179592413;179592412
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: L
• RefSeq wild type transcript codon: TTA
• RefSeq wild type template codon: AAT
• Domain: Ig-50
• Domain position: 58
• Structural Position: 138
• Q(SASA): 0.064
• 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
L/S	None	None	1.0	D	0.888	0.806	0.88376241617	gnomAD-4.0.0	1.36887E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79948E-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
L/A	0.9003	likely_pathogenic	0.8836	pathogenic	-2.581	Highly Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	N
L/C	0.8329	likely_pathogenic	0.8013	pathogenic	-1.705	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
L/D	0.9992	likely_pathogenic	0.999	pathogenic	-3.281	Highly Destabilizing	1.0	D	0.917	deleterious	None	None	None	None	N
L/E	0.9919	likely_pathogenic	0.9914	pathogenic	-2.949	Highly Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
L/F	0.6254	likely_pathogenic	0.6039	pathogenic	-1.567	Destabilizing	1.0	D	0.828	deleterious	D	0.546715315	None	None	N
L/G	0.9817	likely_pathogenic	0.9787	pathogenic	-3.192	Highly Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
L/H	0.9753	likely_pathogenic	0.9759	pathogenic	-2.992	Highly Destabilizing	1.0	D	0.898	deleterious	None	None	None	None	N
L/I	0.2125	likely_benign	0.177	benign	-0.732	Destabilizing	0.999	D	0.685	prob.neutral	N	0.508834511	None	None	N
L/K	0.987	likely_pathogenic	0.9878	pathogenic	-1.91	Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	N
L/M	0.3488	ambiguous	0.3397	benign	-0.927	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	N
L/N	0.9943	likely_pathogenic	0.9934	pathogenic	-2.67	Highly Destabilizing	1.0	D	0.917	deleterious	None	None	None	None	N
L/P	0.9928	likely_pathogenic	0.9931	pathogenic	-1.341	Destabilizing	1.0	D	0.916	deleterious	None	None	None	None	N
L/Q	0.9477	likely_pathogenic	0.9517	pathogenic	-2.269	Highly Destabilizing	1.0	D	0.917	deleterious	None	None	None	None	N
L/R	0.9621	likely_pathogenic	0.9662	pathogenic	-2.115	Highly Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
L/S	0.9818	likely_pathogenic	0.9783	pathogenic	-3.181	Highly Destabilizing	1.0	D	0.888	deleterious	D	0.560264121	None	None	N
L/T	0.9471	likely_pathogenic	0.9394	pathogenic	-2.677	Highly Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
L/V	0.2257	likely_benign	0.2009	benign	-1.341	Destabilizing	0.999	D	0.681	prob.neutral	D	0.546968805	None	None	N
L/W	0.9357	likely_pathogenic	0.9268	pathogenic	-1.95	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
L/Y	0.9634	likely_pathogenic	0.9614	pathogenic	-1.744	Destabilizing	1.0	D	0.875	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.