TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7325	22198;22199;22200	chr2:178722926;178722925;178722924	chr2:179587653;179587652;179587651
N2AB	7008	21247;21248;21249	chr2:178722926;178722925;178722924	chr2:179587653;179587652;179587651
N2A	6081	18466;18467;18468	chr2:178722926;178722925;178722924	chr2:179587653;179587652;179587651
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: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Ig-58
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.1308
• 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
F/L	None	None	0.998	N	0.647	0.713	0.523082183605	gnomAD-4.0.0	1.60027E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.04062E-05
F/V	None	None	0.999	N	0.737	0.712	0.8835682466	gnomAD-4.0.0	6.8582E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00815E-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
F/A	0.9606	likely_pathogenic	0.9891	pathogenic	-2.863	Highly Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
F/C	0.9223	likely_pathogenic	0.977	pathogenic	-1.761	Destabilizing	1.0	D	0.853	deleterious	D	0.558022395	None	None	N
F/D	0.995	likely_pathogenic	0.9984	pathogenic	-2.481	Highly Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
F/E	0.9945	likely_pathogenic	0.9983	pathogenic	-2.385	Highly Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
F/G	0.9879	likely_pathogenic	0.9966	pathogenic	-3.196	Highly Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
F/H	0.9735	likely_pathogenic	0.9887	pathogenic	-1.402	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
F/I	0.548	ambiguous	0.745	pathogenic	-1.819	Destabilizing	0.999	D	0.67	neutral	D	0.526557646	None	None	N
F/K	0.9938	likely_pathogenic	0.9977	pathogenic	-1.548	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
F/L	0.9431	likely_pathogenic	0.9768	pathogenic	-1.819	Destabilizing	0.998	D	0.647	neutral	N	0.505832316	None	None	N
F/M	0.8636	likely_pathogenic	0.9354	pathogenic	-1.604	Destabilizing	0.998	D	0.737	prob.delet.	None	None	None	None	N
F/N	0.9855	likely_pathogenic	0.995	pathogenic	-1.628	Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
F/P	0.9953	likely_pathogenic	0.9986	pathogenic	-2.168	Highly Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
F/Q	0.9911	likely_pathogenic	0.9971	pathogenic	-1.838	Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
F/R	0.9817	likely_pathogenic	0.9927	pathogenic	-0.761	Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
F/S	0.9601	likely_pathogenic	0.9905	pathogenic	-2.377	Highly Destabilizing	1.0	D	0.829	deleterious	D	0.557515416	None	None	N
F/T	0.9608	likely_pathogenic	0.9885	pathogenic	-2.19	Highly Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
F/V	0.6356	likely_pathogenic	0.8112	pathogenic	-2.168	Highly Destabilizing	0.999	D	0.737	prob.delet.	N	0.505894769	None	None	N
F/W	0.8857	likely_pathogenic	0.9383	pathogenic	-0.698	Destabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	N
F/Y	0.6341	likely_pathogenic	0.7526	pathogenic	-0.954	Destabilizing	0.998	D	0.587	neutral	D	0.5464126	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.