TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8182	24769;24770;24771	chr2:178718562;178718561;178718560	chr2:179583289;179583288;179583287
N2AB	7865	23818;23819;23820	chr2:178718562;178718561;178718560	chr2:179583289;179583288;179583287
N2A	6938	21037;21038;21039	chr2:178718562;178718561;178718560	chr2:179583289;179583288;179583287
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: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-67
• Domain position: 12
• Structural Position: 16
• Q(SASA): 0.1879
• 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	0.973	D	0.483	0.493	0.671574616662	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	0.2782	likely_benign	0.2798	benign	-1.633	Destabilizing	0.973	D	0.483	neutral	D	0.538641509	None	None	N
V/C	0.8592	likely_pathogenic	0.8583	pathogenic	-1.66	Destabilizing	1.0	D	0.601	neutral	None	None	None	None	N
V/D	0.8416	likely_pathogenic	0.878	pathogenic	-1.053	Destabilizing	0.998	D	0.701	prob.neutral	D	0.551563934	None	None	N
V/E	0.6819	likely_pathogenic	0.7326	pathogenic	-0.952	Destabilizing	1.0	D	0.647	neutral	None	None	None	None	N
V/F	0.4182	ambiguous	0.4023	ambiguous	-1.15	Destabilizing	0.999	D	0.654	neutral	N	0.521342905	None	None	N
V/G	0.4974	ambiguous	0.5414	ambiguous	-2.023	Highly Destabilizing	0.217	N	0.444	neutral	N	0.515013029	None	None	N
V/H	0.8793	likely_pathogenic	0.8901	pathogenic	-1.528	Destabilizing	1.0	D	0.642	neutral	None	None	None	None	N
V/I	0.0963	likely_benign	0.0897	benign	-0.615	Destabilizing	0.998	D	0.475	neutral	N	0.512225699	None	None	N
V/K	0.6577	likely_pathogenic	0.7054	pathogenic	-1.075	Destabilizing	0.999	D	0.653	neutral	None	None	None	None	N
V/L	0.4038	ambiguous	0.3651	ambiguous	-0.615	Destabilizing	0.996	D	0.481	neutral	N	0.495930815	None	None	N
V/M	0.2453	likely_benign	0.2328	benign	-0.893	Destabilizing	1.0	D	0.631	neutral	None	None	None	None	N
V/N	0.7029	likely_pathogenic	0.7457	pathogenic	-1.082	Destabilizing	0.999	D	0.696	prob.neutral	None	None	None	None	N
V/P	0.9554	likely_pathogenic	0.9585	pathogenic	-0.923	Destabilizing	1.0	D	0.645	neutral	None	None	None	None	N
V/Q	0.6237	likely_pathogenic	0.6805	pathogenic	-1.103	Destabilizing	1.0	D	0.647	neutral	None	None	None	None	N
V/R	0.5935	likely_pathogenic	0.657	pathogenic	-0.856	Destabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	N
V/S	0.453	ambiguous	0.4938	ambiguous	-1.835	Destabilizing	0.998	D	0.643	neutral	None	None	None	None	N
V/T	0.2435	likely_benign	0.2557	benign	-1.598	Destabilizing	0.996	D	0.583	neutral	None	None	None	None	N
V/W	0.9597	likely_pathogenic	0.9568	pathogenic	-1.319	Destabilizing	1.0	D	0.599	neutral	None	None	None	None	N
V/Y	0.868	likely_pathogenic	0.8722	pathogenic	-0.981	Destabilizing	1.0	D	0.651	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.