TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8260	25003;25004;25005	chr2:178718328;178718327;178718326	chr2:179583055;179583054;179583053
N2AB	7943	24052;24053;24054	chr2:178718328;178718327;178718326	chr2:179583055;179583054;179583053
N2A	7016	21271;21272;21273	chr2:178718328;178718327;178718326	chr2:179583055;179583054;179583053
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: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-67
• Domain position: 90
• Structural Position: 177
• Q(SASA): 0.3604
• 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
V/A	None	None	0.939	D	0.603	0.693	0.784858872101	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
V/A	0.5907	likely_pathogenic	0.7551	pathogenic	-1.504	Destabilizing	0.939	D	0.603	neutral	D	0.607838761	None	None	N
V/C	0.9191	likely_pathogenic	0.9525	pathogenic	-1.421	Destabilizing	0.999	D	0.701	prob.neutral	None	None	None	None	N
V/D	0.9409	likely_pathogenic	0.9818	pathogenic	-1.091	Destabilizing	0.997	D	0.715	prob.delet.	D	0.608444174	None	None	N
V/E	0.8711	likely_pathogenic	0.9488	pathogenic	-1.028	Destabilizing	0.998	D	0.692	prob.neutral	None	None	None	None	N
V/F	0.522	ambiguous	0.6631	pathogenic	-1.117	Destabilizing	0.982	D	0.703	prob.neutral	D	0.607838761	None	None	N
V/G	0.7205	likely_pathogenic	0.861	pathogenic	-1.844	Destabilizing	0.997	D	0.694	prob.neutral	D	0.608444174	None	None	N
V/H	0.95	likely_pathogenic	0.981	pathogenic	-1.352	Destabilizing	0.999	D	0.7	prob.neutral	None	None	None	None	N
V/I	0.0853	likely_benign	0.0818	benign	-0.64	Destabilizing	0.046	N	0.461	neutral	N	0.502939786	None	None	N
V/K	0.8788	likely_pathogenic	0.9552	pathogenic	-0.939	Destabilizing	0.993	D	0.692	prob.neutral	None	None	None	None	N
V/L	0.4116	ambiguous	0.5111	ambiguous	-0.64	Destabilizing	0.76	D	0.639	neutral	D	0.564031081	None	None	N
V/M	0.376	ambiguous	0.4765	ambiguous	-0.824	Destabilizing	0.986	D	0.719	prob.delet.	None	None	None	None	N
V/N	0.811	likely_pathogenic	0.9158	pathogenic	-0.875	Destabilizing	0.998	D	0.721	prob.delet.	None	None	None	None	N
V/P	0.865	likely_pathogenic	0.9383	pathogenic	-0.896	Destabilizing	0.998	D	0.704	prob.neutral	None	None	None	None	N
V/Q	0.8683	likely_pathogenic	0.9468	pathogenic	-0.972	Destabilizing	0.998	D	0.713	prob.delet.	None	None	None	None	N
V/R	0.8455	likely_pathogenic	0.9438	pathogenic	-0.671	Destabilizing	0.998	D	0.719	prob.delet.	None	None	None	None	N
V/S	0.7133	likely_pathogenic	0.8542	pathogenic	-1.554	Destabilizing	0.993	D	0.669	neutral	None	None	None	None	N
V/T	0.5201	ambiguous	0.6362	pathogenic	-1.373	Destabilizing	0.953	D	0.67	neutral	None	None	None	None	N
V/W	0.9817	likely_pathogenic	0.9915	pathogenic	-1.274	Destabilizing	0.999	D	0.669	neutral	None	None	None	None	N
V/Y	0.9188	likely_pathogenic	0.9655	pathogenic	-0.936	Destabilizing	0.998	D	0.707	prob.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.