TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8992	27199;27200;27201	chr2:178713160;178713159;178713158	chr2:179577887;179577886;179577885
N2AB	8675	26248;26249;26250	chr2:178713160;178713159;178713158	chr2:179577887;179577886;179577885
N2A	7748	23467;23468;23469	chr2:178713160;178713159;178713158	chr2:179577887;179577886;179577885
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: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-75
• Domain position: 67
• Structural Position: 149
• Q(SASA): 0.1374
• 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/H	None	None	1.0	D	0.861	0.589	0.626919690049	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
D/A	0.8481	likely_pathogenic	0.8974	pathogenic	0.535	Stabilizing	0.992	D	0.813	deleterious	D	0.665928132	None	None	N
D/C	0.9576	likely_pathogenic	0.9668	pathogenic	0.43	Stabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
D/E	0.807	likely_pathogenic	0.8317	pathogenic	-0.621	Destabilizing	0.996	D	0.621	neutral	D	0.619445199	None	None	N
D/F	0.9753	likely_pathogenic	0.9824	pathogenic	1.066	Stabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
D/G	0.8951	likely_pathogenic	0.9271	pathogenic	0.037	Stabilizing	0.996	D	0.791	deleterious	D	0.666129936	None	None	N
D/H	0.8101	likely_pathogenic	0.8378	pathogenic	0.592	Stabilizing	1.0	D	0.861	deleterious	D	0.592503381	None	None	N
D/I	0.9615	likely_pathogenic	0.9737	pathogenic	1.881	Stabilizing	0.998	D	0.884	deleterious	None	None	None	None	N
D/K	0.9644	likely_pathogenic	0.9761	pathogenic	0.155	Stabilizing	0.998	D	0.839	deleterious	None	None	None	None	N
D/L	0.9637	likely_pathogenic	0.9739	pathogenic	1.881	Stabilizing	0.998	D	0.888	deleterious	None	None	None	None	N
D/M	0.981	likely_pathogenic	0.9875	pathogenic	2.337	Highly Stabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
D/N	0.6046	likely_pathogenic	0.6656	pathogenic	-0.635	Destabilizing	0.999	D	0.797	deleterious	D	0.597218113	None	None	N
D/P	0.9905	likely_pathogenic	0.9934	pathogenic	1.463	Stabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
D/Q	0.9349	likely_pathogenic	0.95	pathogenic	-0.215	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
D/R	0.9683	likely_pathogenic	0.976	pathogenic	0.021	Stabilizing	0.999	D	0.885	deleterious	None	None	None	None	N
D/S	0.717	likely_pathogenic	0.7834	pathogenic	-0.979	Destabilizing	0.988	D	0.669	neutral	None	None	None	None	N
D/T	0.9248	likely_pathogenic	0.9452	pathogenic	-0.515	Destabilizing	0.833	D	0.501	neutral	None	None	None	None	N
D/V	0.8987	likely_pathogenic	0.9251	pathogenic	1.463	Stabilizing	0.998	D	0.887	deleterious	D	0.666533545	None	None	N
D/W	0.9958	likely_pathogenic	0.9968	pathogenic	0.949	Stabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
D/Y	0.8716	likely_pathogenic	0.9038	pathogenic	1.296	Stabilizing	1.0	D	0.908	deleterious	D	0.628953231	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.