TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27759	83500;83501;83502	chr2:178562857;178562856;178562855	chr2:179427584;179427583;179427582
N2AB	26118	78577;78578;78579	chr2:178562857;178562856;178562855	chr2:179427584;179427583;179427582
N2A	25191	75796;75797;75798	chr2:178562857;178562856;178562855	chr2:179427584;179427583;179427582
N2B	18694	56305;56306;56307	chr2:178562857;178562856;178562855	chr2:179427584;179427583;179427582
Novex-1	18819	56680;56681;56682	chr2:178562857;178562856;178562855	chr2:179427584;179427583;179427582
Novex-2	18886	56881;56882;56883	chr2:178562857;178562856;178562855	chr2:179427584;179427583;179427582
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-141
• Domain position: 84
• Structural Position: 172
• Q(SASA): 0.1232
• 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	rs749582041	-0.345	0.046	N	0.21	0.157	None	gnomAD-2.1.1	1.08E-05	None	None	None	None	N	None	8.33E-05	0	None	0	0	None	0	None	0	0	1.41683E-04
V/I	rs749582041	-0.345	0.046	N	0.21	0.157	None	gnomAD-3.1.2	3.29E-05	None	None	None	None	N	None	1.2075E-04	0	0	0	0	None	0	0	0	0	0
V/I	rs749582041	-0.345	0.046	N	0.21	0.157	None	gnomAD-4.0.0	4.96027E-06	None	None	None	None	N	None	1.06855E-04	0	None	0	0	None	0	0	0	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	0.8978	likely_pathogenic	0.9185	pathogenic	-1.735	Destabilizing	0.939	D	0.519	neutral	N	0.491627358	None	None	N
V/C	0.9231	likely_pathogenic	0.9334	pathogenic	-1.227	Destabilizing	0.999	D	0.778	deleterious	None	None	None	None	N
V/D	0.9985	likely_pathogenic	0.999	pathogenic	-2.468	Highly Destabilizing	0.997	D	0.841	deleterious	D	0.529199583	None	None	N
V/E	0.9956	likely_pathogenic	0.9968	pathogenic	-2.145	Highly Destabilizing	0.998	D	0.801	deleterious	None	None	None	None	N
V/F	0.8068	likely_pathogenic	0.8419	pathogenic	-0.924	Destabilizing	0.982	D	0.787	deleterious	D	0.536081207	None	None	N
V/G	0.9568	likely_pathogenic	0.9661	pathogenic	-2.37	Highly Destabilizing	0.997	D	0.821	deleterious	N	0.510841838	None	None	N
V/H	0.9973	likely_pathogenic	0.998	pathogenic	-2.413	Highly Destabilizing	0.999	D	0.837	deleterious	None	None	None	None	N
V/I	0.0964	likely_benign	0.0973	benign	0.09	Stabilizing	0.046	N	0.21	neutral	N	0.457657708	None	None	N
V/K	0.9953	likely_pathogenic	0.9965	pathogenic	-1.263	Destabilizing	0.993	D	0.805	deleterious	None	None	None	None	N
V/L	0.6315	likely_pathogenic	0.6901	pathogenic	0.09	Stabilizing	0.76	D	0.471	neutral	N	0.511220047	None	None	N
V/M	0.758	likely_pathogenic	0.7981	pathogenic	-0.166	Destabilizing	0.986	D	0.712	prob.delet.	None	None	None	None	N
V/N	0.9931	likely_pathogenic	0.9947	pathogenic	-1.896	Destabilizing	0.998	D	0.855	deleterious	None	None	None	None	N
V/P	0.9952	likely_pathogenic	0.9969	pathogenic	-0.495	Destabilizing	0.998	D	0.821	deleterious	None	None	None	None	N
V/Q	0.9914	likely_pathogenic	0.9933	pathogenic	-1.502	Destabilizing	0.998	D	0.828	deleterious	None	None	None	None	N
V/R	0.988	likely_pathogenic	0.9906	pathogenic	-1.571	Destabilizing	0.998	D	0.856	deleterious	None	None	None	None	N
V/S	0.9691	likely_pathogenic	0.9759	pathogenic	-2.482	Highly Destabilizing	0.993	D	0.796	deleterious	None	None	None	None	N
V/T	0.922	likely_pathogenic	0.9366	pathogenic	-1.977	Destabilizing	0.953	D	0.629	neutral	None	None	None	None	N
V/W	0.9966	likely_pathogenic	0.9973	pathogenic	-1.498	Destabilizing	0.999	D	0.826	deleterious	None	None	None	None	N
V/Y	0.9879	likely_pathogenic	0.9912	pathogenic	-1.057	Destabilizing	0.998	D	0.799	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.