TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8395	25408;25409;25410	chr2:178717691;178717690;178717689	chr2:179582418;179582417;179582416
N2AB	8078	24457;24458;24459	chr2:178717691;178717690;178717689	chr2:179582418;179582417;179582416
N2A	7151	21676;21677;21678	chr2:178717691;178717690;178717689	chr2:179582418;179582417;179582416
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: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-69
• Domain position: 36
• Structural Position: 50
• Q(SASA): 0.2854
• 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/E	None	None	1.0	N	0.637	0.529	0.275215494804	gnomAD-4.0.0	1.59208E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02645E-05

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	0.9634	likely_pathogenic	0.9737	pathogenic	-1.059	Destabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	N
K/C	0.9527	likely_pathogenic	0.9625	pathogenic	-1.094	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
K/D	0.9956	likely_pathogenic	0.9972	pathogenic	-0.333	Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	N
K/E	0.8951	likely_pathogenic	0.9233	pathogenic	-0.172	Destabilizing	1.0	D	0.637	neutral	N	0.519899018	None	None	N
K/F	0.977	likely_pathogenic	0.9837	pathogenic	-0.779	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
K/G	0.9825	likely_pathogenic	0.9885	pathogenic	-1.452	Destabilizing	1.0	D	0.734	prob.delet.	None	None	None	None	N
K/H	0.7063	likely_pathogenic	0.7107	pathogenic	-1.748	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
K/I	0.9054	likely_pathogenic	0.9275	pathogenic	-0.012	Destabilizing	0.999	D	0.82	deleterious	None	None	None	None	N
K/L	0.864	likely_pathogenic	0.8879	pathogenic	-0.012	Destabilizing	0.999	D	0.734	prob.delet.	None	None	None	None	N
K/M	0.8008	likely_pathogenic	0.8441	pathogenic	-0.091	Destabilizing	1.0	D	0.766	deleterious	N	0.508289223	None	None	N
K/N	0.9795	likely_pathogenic	0.9855	pathogenic	-0.813	Destabilizing	1.0	D	0.7	prob.neutral	N	0.501959348	None	None	N
K/P	0.9978	likely_pathogenic	0.9988	pathogenic	-0.333	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
K/Q	0.564	likely_pathogenic	0.6062	pathogenic	-0.832	Destabilizing	1.0	D	0.681	prob.neutral	N	0.487716206	None	None	N
K/R	0.0987	likely_benign	0.1017	benign	-0.694	Destabilizing	1.0	D	0.629	neutral	N	0.493873067	None	None	N
K/S	0.9788	likely_pathogenic	0.9858	pathogenic	-1.601	Destabilizing	1.0	D	0.656	neutral	None	None	None	None	N
K/T	0.9463	likely_pathogenic	0.9624	pathogenic	-1.207	Destabilizing	1.0	D	0.724	prob.delet.	N	0.507782244	None	None	N
K/V	0.888	likely_pathogenic	0.9073	pathogenic	-0.333	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	N
K/W	0.9603	likely_pathogenic	0.9691	pathogenic	-0.606	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
K/Y	0.9311	likely_pathogenic	0.9466	pathogenic	-0.286	Destabilizing	1.0	D	0.797	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.