TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9263	28012;28013;28014	chr2:178712043;178712042;178712041	chr2:179576770;179576769;179576768
N2AB	8946	27061;27062;27063	chr2:178712043;178712042;178712041	chr2:179576770;179576769;179576768
N2A	8019	24280;24281;24282	chr2:178712043;178712042;178712041	chr2:179576770;179576769;179576768
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-78
• Domain position: 59
• Structural Position: 139
• Q(SASA): 0.2641
• 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	0.826	D	0.463	0.259	0.63498429051	gnomAD-4.0.0	1.59131E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43295E-05	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	0.2021	likely_benign	0.3131	benign	-1.786	Destabilizing	0.826	D	0.463	neutral	D	0.526728218	None	None	N
V/C	0.7769	likely_pathogenic	0.8615	pathogenic	-1.419	Destabilizing	0.999	D	0.517	neutral	None	None	None	None	N
V/D	0.3539	ambiguous	0.5456	ambiguous	-1.842	Destabilizing	0.988	D	0.591	neutral	N	0.488859562	None	None	N
V/E	0.2843	likely_benign	0.3807	ambiguous	-1.714	Destabilizing	0.939	D	0.547	neutral	None	None	None	None	N
V/F	0.1589	likely_benign	0.2573	benign	-1.147	Destabilizing	0.996	D	0.537	neutral	N	0.509662609	None	None	N
V/G	0.2714	likely_benign	0.4624	ambiguous	-2.248	Highly Destabilizing	0.959	D	0.563	neutral	N	0.504254792	None	None	N
V/H	0.4856	ambiguous	0.611	pathogenic	-1.892	Destabilizing	0.999	D	0.599	neutral	None	None	None	None	N
V/I	0.0779	likely_benign	0.0885	benign	-0.551	Destabilizing	0.826	D	0.521	neutral	N	0.493442363	None	None	N
V/K	0.4272	ambiguous	0.5183	ambiguous	-1.411	Destabilizing	0.079	N	0.414	neutral	None	None	None	None	N
V/L	0.1842	likely_benign	0.2679	benign	-0.551	Destabilizing	0.826	D	0.519	neutral	N	0.503928716	None	None	N
V/M	0.1647	likely_benign	0.2297	benign	-0.575	Destabilizing	0.997	D	0.502	neutral	None	None	None	None	N
V/N	0.2534	likely_benign	0.3922	ambiguous	-1.476	Destabilizing	0.991	D	0.593	neutral	None	None	None	None	N
V/P	0.9409	likely_pathogenic	0.9813	pathogenic	-0.931	Destabilizing	0.997	D	0.561	neutral	None	None	None	None	N
V/Q	0.3153	likely_benign	0.3946	ambiguous	-1.457	Destabilizing	0.982	D	0.556	neutral	None	None	None	None	N
V/R	0.3488	ambiguous	0.4382	ambiguous	-1.128	Destabilizing	0.884	D	0.573	neutral	None	None	None	None	N
V/S	0.1888	likely_benign	0.2836	benign	-2.136	Highly Destabilizing	0.884	D	0.555	neutral	None	None	None	None	N
V/T	0.1841	likely_benign	0.2457	benign	-1.871	Destabilizing	0.17	N	0.242	neutral	None	None	None	None	N
V/W	0.817	likely_pathogenic	0.9081	pathogenic	-1.518	Destabilizing	0.999	D	0.638	neutral	None	None	None	None	N
V/Y	0.493	ambiguous	0.6229	pathogenic	-1.154	Destabilizing	0.997	D	0.545	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.