TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5040	15343;15344;15345	chr2:178734806;178734805;178734804	chr2:179599533;179599532;179599531
N2AB	4723	14392;14393;14394	chr2:178734806;178734805;178734804	chr2:179599533;179599532;179599531
N2A	3796	11611;11612;11613	chr2:178734806;178734805;178734804	chr2:179599533;179599532;179599531
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: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-33
• Domain position: 60
• Structural Position: 139
• Q(SASA): 0.3075
• 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
D/G	rs1315700657	None	0.811	N	0.573	0.33	0.32714864917	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	2.75482E-04	None	0	0	0	0	0
D/H	None	None	0.984	N	0.657	0.341	0.3085936734	gnomAD-4.0.0	1.36843E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79896E-06	0	0
D/Y	None	None	0.995	N	0.722	0.414	0.604632981478	gnomAD-4.0.0	1.36843E-06	None	None	None	None	N	None	0	0	None	0	5.03981E-05	None	0	0	0	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
D/A	0.3182	likely_benign	0.2688	benign	-0.227	Destabilizing	0.896	D	0.611	neutral	N	0.476770284	None	None	N
D/C	0.804	likely_pathogenic	0.742	pathogenic	-0.054	Destabilizing	0.999	D	0.739	prob.delet.	None	None	None	None	N
D/E	0.2113	likely_benign	0.1746	benign	-0.635	Destabilizing	0.046	N	0.201	neutral	N	0.365077199	None	None	N
D/F	0.6982	likely_pathogenic	0.6365	pathogenic	0.253	Stabilizing	0.996	D	0.718	prob.delet.	None	None	None	None	N
D/G	0.4449	ambiguous	0.3649	ambiguous	-0.683	Destabilizing	0.811	D	0.573	neutral	N	0.504105685	None	None	N
D/H	0.3755	ambiguous	0.3071	benign	-0.123	Destabilizing	0.984	D	0.657	neutral	N	0.452462347	None	None	N
D/I	0.4644	ambiguous	0.4121	ambiguous	1.014	Stabilizing	0.988	D	0.723	prob.delet.	None	None	None	None	N
D/K	0.7119	likely_pathogenic	0.5838	pathogenic	-0.49	Destabilizing	0.919	D	0.569	neutral	None	None	None	None	N
D/L	0.526	ambiguous	0.47	ambiguous	1.014	Stabilizing	0.988	D	0.679	prob.neutral	None	None	None	None	N
D/M	0.723	likely_pathogenic	0.6798	pathogenic	1.512	Stabilizing	0.999	D	0.714	prob.delet.	None	None	None	None	N
D/N	0.1455	likely_benign	0.135	benign	-0.98	Destabilizing	0.026	N	0.373	neutral	N	0.437854668	None	None	N
D/P	0.9871	likely_pathogenic	0.9792	pathogenic	0.628	Stabilizing	0.996	D	0.631	neutral	None	None	None	None	N
D/Q	0.5232	ambiguous	0.4369	ambiguous	-0.657	Destabilizing	0.919	D	0.536	neutral	None	None	None	None	N
D/R	0.7123	likely_pathogenic	0.5858	pathogenic	-0.501	Destabilizing	0.976	D	0.645	neutral	None	None	None	None	N
D/S	0.2213	likely_benign	0.1936	benign	-1.433	Destabilizing	0.851	D	0.56	neutral	None	None	None	None	N
D/T	0.4059	ambiguous	0.3497	ambiguous	-1.022	Destabilizing	0.919	D	0.573	neutral	None	None	None	None	N
D/V	0.2771	likely_benign	0.2474	benign	0.628	Stabilizing	0.984	D	0.681	prob.neutral	N	0.415064886	None	None	N
D/W	0.9351	likely_pathogenic	0.9056	pathogenic	0.209	Stabilizing	0.999	D	0.699	prob.neutral	None	None	None	None	N
D/Y	0.3189	likely_benign	0.2591	benign	0.478	Stabilizing	0.995	D	0.722	prob.delet.	N	0.488030214	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.