TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8772	26539;26540;26541	chr2:178714460;178714459;178714458	chr2:179579187;179579186;179579185
N2AB	8455	25588;25589;25590	chr2:178714460;178714459;178714458	chr2:179579187;179579186;179579185
N2A	7528	22807;22808;22809	chr2:178714460;178714459;178714458	chr2:179579187;179579186;179579185
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-73
• Domain position: 37
• Structural Position: 51
• Q(SASA): 0.3957
• 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/V	None	None	0.682	N	0.713	0.404	0.42828666871	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	None	0	0	0	0	0
D/Y	None	None	0.997	N	0.707	0.447	0.617940983249	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31251E-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	0.29	likely_benign	0.387	ambiguous	-0.594	Destabilizing	0.328	N	0.557	neutral	N	0.491325328	None	None	N
D/C	0.7919	likely_pathogenic	0.8702	pathogenic	-0.243	Destabilizing	0.968	D	0.709	prob.delet.	None	None	None	None	N
D/E	0.1547	likely_benign	0.1833	benign	-0.421	Destabilizing	None	N	0.276	neutral	N	0.461571599	None	None	N
D/F	0.7333	likely_pathogenic	0.8293	pathogenic	-0.168	Destabilizing	0.997	D	0.705	prob.neutral	None	None	None	None	N
D/G	0.1259	likely_benign	0.162	benign	-0.894	Destabilizing	0.002	N	0.343	neutral	N	0.47336875	None	None	N
D/H	0.4936	ambiguous	0.6074	pathogenic	-0.303	Destabilizing	0.972	D	0.589	neutral	N	0.507961553	None	None	N
D/I	0.6225	likely_pathogenic	0.7552	pathogenic	0.185	Stabilizing	0.971	D	0.717	prob.delet.	None	None	None	None	N
D/K	0.5866	likely_pathogenic	0.6936	pathogenic	-0.217	Destabilizing	0.89	D	0.52	neutral	None	None	None	None	N
D/L	0.5562	ambiguous	0.6857	pathogenic	0.185	Stabilizing	0.942	D	0.709	prob.delet.	None	None	None	None	N
D/M	0.7412	likely_pathogenic	0.8383	pathogenic	0.49	Stabilizing	0.993	D	0.708	prob.delet.	None	None	None	None	N
D/N	0.1227	likely_benign	0.1554	benign	-0.64	Destabilizing	0.604	D	0.498	neutral	N	0.486664667	None	None	N
D/P	0.9041	likely_pathogenic	0.9426	pathogenic	-0.051	Destabilizing	0.394	N	0.591	neutral	None	None	None	None	N
D/Q	0.461	ambiguous	0.5659	pathogenic	-0.526	Destabilizing	0.752	D	0.556	neutral	None	None	None	None	N
D/R	0.6127	likely_pathogenic	0.7137	pathogenic	0.015	Stabilizing	0.942	D	0.643	neutral	None	None	None	None	N
D/S	0.192	likely_benign	0.2607	benign	-0.832	Destabilizing	0.393	N	0.443	neutral	None	None	None	None	N
D/T	0.4523	ambiguous	0.5813	pathogenic	-0.587	Destabilizing	0.669	D	0.539	neutral	None	None	None	None	N
D/V	0.3891	ambiguous	0.5257	ambiguous	-0.051	Destabilizing	0.682	D	0.713	prob.delet.	N	0.508215042	None	None	N
D/W	0.9108	likely_pathogenic	0.9475	pathogenic	0.068	Stabilizing	0.997	D	0.694	prob.neutral	None	None	None	None	N
D/Y	0.3507	ambiguous	0.4649	ambiguous	0.074	Stabilizing	0.997	D	0.707	prob.neutral	N	0.508215042	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.