TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2591	7996;7997;7998	chr2:178773193;178773192;178773191	chr2:179637920;179637919;179637918
N2AB	2591	7996;7997;7998	chr2:178773193;178773192;178773191	chr2:179637920;179637919;179637918
N2A	2591	7996;7997;7998	chr2:178773193;178773192;178773191	chr2:179637920;179637919;179637918
N2B	2545	7858;7859;7860	chr2:178773193;178773192;178773191	chr2:179637920;179637919;179637918
Novex-1	2545	7858;7859;7860	chr2:178773193;178773192;178773191	chr2:179637920;179637919;179637918
Novex-2	2545	7858;7859;7860	chr2:178773193;178773192;178773191	chr2:179637920;179637919;179637918
Novex-3	2591	7996;7997;7998	chr2:178773193;178773192;178773191	chr2:179637920;179637919;179637918

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-15
• Domain position: 59
• Structural Position: 140
• Q(SASA): 0.0759
• 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/I	None	None	0.003	N	0.235	0.073	0.229924730088	gnomAD-4.0.0	1.36848E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79884E-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	0.6208	likely_pathogenic	0.6545	pathogenic	-2.254	Highly Destabilizing	0.517	D	0.619	neutral	D	0.587007148	None	None	N
V/C	0.9106	likely_pathogenic	0.9152	pathogenic	-1.708	Destabilizing	0.996	D	0.781	deleterious	None	None	None	None	N
V/D	0.976	likely_pathogenic	0.9749	pathogenic	-3.288	Highly Destabilizing	0.983	D	0.884	deleterious	D	0.588397624	None	None	N
V/E	0.9412	likely_pathogenic	0.9414	pathogenic	-2.969	Highly Destabilizing	0.987	D	0.865	deleterious	None	None	None	None	N
V/F	0.5422	ambiguous	0.5472	ambiguous	-1.224	Destabilizing	0.901	D	0.783	deleterious	N	0.514037374	None	None	N
V/G	0.8022	likely_pathogenic	0.8106	pathogenic	-2.849	Highly Destabilizing	0.949	D	0.875	deleterious	D	0.588397624	None	None	N
V/H	0.9707	likely_pathogenic	0.9709	pathogenic	-2.862	Highly Destabilizing	0.996	D	0.88	deleterious	None	None	None	None	N
V/I	0.0881	likely_benign	0.0947	benign	-0.513	Destabilizing	0.003	N	0.235	neutral	N	0.370014603	None	None	N
V/K	0.9474	likely_pathogenic	0.9439	pathogenic	-1.799	Destabilizing	0.961	D	0.863	deleterious	None	None	None	None	N
V/L	0.3603	ambiguous	0.3949	ambiguous	-0.513	Destabilizing	0.075	N	0.372	neutral	N	0.477434028	None	None	N
V/M	0.3691	ambiguous	0.4002	ambiguous	-0.85	Destabilizing	0.923	D	0.682	prob.neutral	None	None	None	None	N
V/N	0.9313	likely_pathogenic	0.9323	pathogenic	-2.497	Highly Destabilizing	0.987	D	0.889	deleterious	None	None	None	None	N
V/P	0.9752	likely_pathogenic	0.9749	pathogenic	-1.076	Destabilizing	0.987	D	0.868	deleterious	None	None	None	None	N
V/Q	0.9365	likely_pathogenic	0.937	pathogenic	-2.111	Highly Destabilizing	0.987	D	0.895	deleterious	None	None	None	None	N
V/R	0.9259	likely_pathogenic	0.9223	pathogenic	-1.966	Destabilizing	0.987	D	0.889	deleterious	None	None	None	None	N
V/S	0.8498	likely_pathogenic	0.8571	pathogenic	-2.953	Highly Destabilizing	0.961	D	0.841	deleterious	None	None	None	None	N
V/T	0.7747	likely_pathogenic	0.7884	pathogenic	-2.48	Highly Destabilizing	0.775	D	0.661	neutral	None	None	None	None	N
V/W	0.9857	likely_pathogenic	0.9864	pathogenic	-1.846	Destabilizing	0.996	D	0.873	deleterious	None	None	None	None	N
V/Y	0.9241	likely_pathogenic	0.9226	pathogenic	-1.532	Destabilizing	0.961	D	0.781	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.