TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23764	71515;71516;71517	chr2:178574842;178574841;178574840	chr2:179439569;179439568;179439567
N2AB	22123	66592;66593;66594	chr2:178574842;178574841;178574840	chr2:179439569;179439568;179439567
N2A	21196	63811;63812;63813	chr2:178574842;178574841;178574840	chr2:179439569;179439568;179439567
N2B	14699	44320;44321;44322	chr2:178574842;178574841;178574840	chr2:179439569;179439568;179439567
Novex-1	14824	44695;44696;44697	chr2:178574842;178574841;178574840	chr2:179439569;179439568;179439567
Novex-2	14891	44896;44897;44898	chr2:178574842;178574841;178574840	chr2:179439569;179439568;179439567
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Fn3-60
• Domain position: 39
• Structural Position: 40
• Q(SASA): 0.0902
• 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/M	rs773302092	-0.923	0.982	N	0.691	0.357	0.609194942736	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	2.91E-05	None	0	0	None	0	None	0	0	0
V/M	rs773302092	-0.923	0.982	N	0.691	0.357	0.609194942736	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	0.8121	likely_pathogenic	0.8194	pathogenic	-2.305	Highly Destabilizing	0.939	D	0.605	neutral	D	0.528639697	None	None	N
V/C	0.9612	likely_pathogenic	0.9623	pathogenic	-1.655	Destabilizing	0.999	D	0.792	deleterious	None	None	None	None	N
V/D	0.999	likely_pathogenic	0.9992	pathogenic	-3.242	Highly Destabilizing	0.998	D	0.892	deleterious	None	None	None	None	N
V/E	0.9962	likely_pathogenic	0.997	pathogenic	-2.902	Highly Destabilizing	0.997	D	0.885	deleterious	D	0.552277361	None	None	N
V/F	0.9121	likely_pathogenic	0.9328	pathogenic	-1.273	Destabilizing	0.986	D	0.809	deleterious	None	None	None	None	N
V/G	0.9558	likely_pathogenic	0.9614	pathogenic	-2.922	Highly Destabilizing	0.997	D	0.901	deleterious	D	0.552277361	None	None	N
V/H	0.999	likely_pathogenic	0.9992	pathogenic	-2.881	Highly Destabilizing	0.999	D	0.881	deleterious	None	None	None	None	N
V/I	0.0947	likely_benign	0.1016	benign	-0.481	Destabilizing	0.06	N	0.255	neutral	None	None	None	None	N
V/K	0.9967	likely_pathogenic	0.9975	pathogenic	-1.761	Destabilizing	0.993	D	0.887	deleterious	None	None	None	None	N
V/L	0.4562	ambiguous	0.5057	ambiguous	-0.481	Destabilizing	0.76	D	0.493	neutral	D	0.52549328	None	None	N
V/M	0.6437	likely_pathogenic	0.6897	pathogenic	-0.86	Destabilizing	0.982	D	0.691	prob.neutral	N	0.510788932	None	None	N
V/N	0.9963	likely_pathogenic	0.9972	pathogenic	-2.552	Highly Destabilizing	0.998	D	0.904	deleterious	None	None	None	None	N
V/P	0.996	likely_pathogenic	0.9969	pathogenic	-1.074	Destabilizing	0.998	D	0.889	deleterious	None	None	None	None	N
V/Q	0.9953	likely_pathogenic	0.9964	pathogenic	-2.118	Highly Destabilizing	0.998	D	0.905	deleterious	None	None	None	None	N
V/R	0.9933	likely_pathogenic	0.9948	pathogenic	-2.044	Highly Destabilizing	0.998	D	0.908	deleterious	None	None	None	None	N
V/S	0.9772	likely_pathogenic	0.9794	pathogenic	-2.992	Highly Destabilizing	0.993	D	0.885	deleterious	None	None	None	None	N
V/T	0.8681	likely_pathogenic	0.8815	pathogenic	-2.483	Highly Destabilizing	0.953	D	0.683	prob.neutral	None	None	None	None	N
V/W	0.9989	likely_pathogenic	0.9991	pathogenic	-1.769	Destabilizing	0.999	D	0.848	deleterious	None	None	None	None	N
V/Y	0.9955	likely_pathogenic	0.9965	pathogenic	-1.516	Destabilizing	0.998	D	0.811	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.