TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24527	73804;73805;73806	chr2:178572553;178572552;178572551	chr2:179437280;179437279;179437278
N2AB	22886	68881;68882;68883	chr2:178572553;178572552;178572551	chr2:179437280;179437279;179437278
N2A	21959	66100;66101;66102	chr2:178572553;178572552;178572551	chr2:179437280;179437279;179437278
N2B	15462	46609;46610;46611	chr2:178572553;178572552;178572551	chr2:179437280;179437279;179437278
Novex-1	15587	46984;46985;46986	chr2:178572553;178572552;178572551	chr2:179437280;179437279;179437278
Novex-2	15654	47185;47186;47187	chr2:178572553;178572552;178572551	chr2:179437280;179437279;179437278
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-66
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.2354
• 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
K/N	rs763480481	-0.255	0.954	D	0.575	0.114	0.224531998449	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
K/N	rs763480481	-0.255	0.954	D	0.575	0.114	0.224531998449	gnomAD-4.0.0	6.84344E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99577E-07	0	0
K/T	None	None	0.04	N	0.343	0.177	0.231873229951	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.9375E-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
K/A	0.2516	likely_benign	0.2331	benign	-0.345	Destabilizing	0.849	D	0.45	neutral	None	None	None	None	N
K/C	0.379	ambiguous	0.3955	ambiguous	-0.498	Destabilizing	0.999	D	0.494	neutral	None	None	None	None	N
K/D	0.6101	likely_pathogenic	0.5486	ambiguous	0.124	Stabilizing	0.965	D	0.571	neutral	None	None	None	None	N
K/E	0.1974	likely_benign	0.1699	benign	0.21	Stabilizing	0.862	D	0.511	neutral	N	0.479963273	None	None	N
K/F	0.5957	likely_pathogenic	0.5604	ambiguous	-0.16	Destabilizing	0.017	N	0.422	neutral	None	None	None	None	N
K/G	0.4501	ambiguous	0.3982	ambiguous	-0.671	Destabilizing	0.965	D	0.531	neutral	None	None	None	None	N
K/H	0.1747	likely_benign	0.1813	benign	-0.955	Destabilizing	0.992	D	0.549	neutral	None	None	None	None	N
K/I	0.2246	likely_benign	0.2077	benign	0.474	Stabilizing	0.005	N	0.438	neutral	None	None	None	None	N
K/L	0.2525	likely_benign	0.2231	benign	0.474	Stabilizing	0.035	N	0.404	neutral	None	None	None	None	N
K/M	0.1772	likely_benign	0.1577	benign	0.238	Stabilizing	0.099	N	0.337	neutral	N	0.476069727	None	None	N
K/N	0.3897	ambiguous	0.3332	benign	-0.256	Destabilizing	0.954	D	0.575	neutral	D	0.523484764	None	None	N
K/P	0.9325	likely_pathogenic	0.8888	pathogenic	0.232	Stabilizing	0.997	D	0.595	neutral	None	None	None	None	N
K/Q	0.1007	likely_benign	0.0976	benign	-0.331	Destabilizing	0.898	D	0.577	neutral	N	0.448832289	None	None	N
K/R	0.0732	likely_benign	0.0731	benign	-0.421	Destabilizing	0.794	D	0.515	neutral	N	0.439770089	None	None	N
K/S	0.3188	likely_benign	0.2909	benign	-0.888	Destabilizing	0.872	D	0.485	neutral	None	None	None	None	N
K/T	0.1211	likely_benign	0.1164	benign	-0.604	Destabilizing	0.04	N	0.343	neutral	N	0.413314206	None	None	N
K/V	0.1966	likely_benign	0.1858	benign	0.232	Stabilizing	0.098	N	0.453	neutral	None	None	None	None	N
K/W	0.6005	likely_pathogenic	0.5818	pathogenic	-0.067	Destabilizing	0.999	D	0.496	neutral	None	None	None	None	N
K/Y	0.4988	ambiguous	0.4778	ambiguous	0.238	Stabilizing	0.526	D	0.566	neutral	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.