TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9551	28876;28877;28878	chr2:178709668;178709667;178709666	chr2:179574395;179574394;179574393
N2AB	9234	27925;27926;27927	chr2:178709668;178709667;178709666	chr2:179574395;179574394;179574393
N2A	8307	25144;25145;25146	chr2:178709668;178709667;178709666	chr2:179574395;179574394;179574393
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: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-81
• Domain position: 59
• Structural Position: 138
• Q(SASA): 0.0771
• 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/P	None	None	1.0	None	0.91	0.859	0.908716035956	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	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
L/A	0.934	likely_pathogenic	0.9324	pathogenic	-2.686	Highly Destabilizing	0.999	D	0.762	deleterious	None	None	None	None	N
L/C	0.8325	likely_pathogenic	0.8597	pathogenic	-1.986	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
L/D	0.9995	likely_pathogenic	0.9997	pathogenic	-3.624	Highly Destabilizing	1.0	D	0.909	deleterious	None	None	None	None	N
L/E	0.9963	likely_pathogenic	0.9972	pathogenic	-3.316	Highly Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
L/F	0.303	likely_benign	0.342	ambiguous	-1.752	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
L/G	0.9825	likely_pathogenic	0.986	pathogenic	-3.253	Highly Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
L/H	0.974	likely_pathogenic	0.9838	pathogenic	-2.964	Highly Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
L/I	0.2457	likely_benign	0.2153	benign	-0.975	Destabilizing	0.999	D	0.689	prob.neutral	None	None	None	None	N
L/K	0.9912	likely_pathogenic	0.9942	pathogenic	-2.294	Highly Destabilizing	1.0	D	0.876	deleterious	None	None	None	None	N
L/M	0.2136	likely_benign	0.2273	benign	-1.087	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
L/N	0.9962	likely_pathogenic	0.9975	pathogenic	-3.033	Highly Destabilizing	1.0	D	0.912	deleterious	None	None	None	None	N
L/P	0.9977	likely_pathogenic	0.9982	pathogenic	-1.538	Destabilizing	1.0	D	0.91	deleterious	None	None	None	None	N
L/Q	0.9697	likely_pathogenic	0.9793	pathogenic	-2.703	Highly Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
L/R	0.9781	likely_pathogenic	0.9848	pathogenic	-2.32	Highly Destabilizing	1.0	D	0.892	deleterious	None	None	None	None	N
L/S	0.9862	likely_pathogenic	0.9889	pathogenic	-3.521	Highly Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
L/T	0.9694	likely_pathogenic	0.9701	pathogenic	-3.054	Highly Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
L/V	0.3166	likely_benign	0.2674	benign	-1.538	Destabilizing	0.999	D	0.693	prob.neutral	None	None	None	None	N
L/W	0.8739	likely_pathogenic	0.9059	pathogenic	-2.157	Highly Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
L/Y	0.9005	likely_pathogenic	0.9269	pathogenic	-1.927	Destabilizing	1.0	D	0.856	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.