TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32353	97282;97283;97284	chr2:178542797;178542796;178542795	chr2:179407524;179407523;179407522
N2AB	30712	92359;92360;92361	chr2:178542797;178542796;178542795	chr2:179407524;179407523;179407522
N2A	29785	89578;89579;89580	chr2:178542797;178542796;178542795	chr2:179407524;179407523;179407522
N2B	23288	70087;70088;70089	chr2:178542797;178542796;178542795	chr2:179407524;179407523;179407522
Novex-1	23413	70462;70463;70464	chr2:178542797;178542796;178542795	chr2:179407524;179407523;179407522
Novex-2	23480	70663;70664;70665	chr2:178542797;178542796;178542795	chr2:179407524;179407523;179407522
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-154
• Domain position: 47
• Structural Position: 121
• Q(SASA): 0.1604
• 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	rs1250490166	-0.724	0.003	N	0.217	0.053	0.313210971179	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.57E-05	None	0	None	0	0	0
V/I	rs1250490166	-0.724	0.003	N	0.217	0.053	0.313210971179	gnomAD-4.0.0	1.36841E-06	None	None	None	None	N	None	0	0	None	0	2.51915E-05	None	0	0	8.99473E-07	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	0.4052	ambiguous	0.3392	benign	-1.825	Destabilizing	0.517	D	0.547	neutral	N	0.50044848	None	None	N
V/C	0.7069	likely_pathogenic	0.6963	pathogenic	-1.422	Destabilizing	0.996	D	0.71	prob.delet.	None	None	None	None	N
V/D	0.8038	likely_pathogenic	0.7504	pathogenic	-1.917	Destabilizing	0.983	D	0.813	deleterious	N	0.49791537	None	None	N
V/E	0.6602	likely_pathogenic	0.5788	pathogenic	-1.863	Destabilizing	0.987	D	0.775	deleterious	None	None	None	None	N
V/F	0.2091	likely_benign	0.1825	benign	-1.34	Destabilizing	0.901	D	0.745	deleterious	N	0.499061614	None	None	N
V/G	0.4731	ambiguous	0.4131	ambiguous	-2.213	Highly Destabilizing	0.949	D	0.777	deleterious	N	0.496901412	None	None	N
V/H	0.7796	likely_pathogenic	0.7442	pathogenic	-1.814	Destabilizing	0.996	D	0.792	deleterious	None	None	None	None	N
V/I	0.0777	likely_benign	0.0717	benign	-0.825	Destabilizing	0.003	N	0.217	neutral	N	0.431452542	None	None	N
V/K	0.7164	likely_pathogenic	0.6486	pathogenic	-1.567	Destabilizing	0.961	D	0.778	deleterious	None	None	None	None	N
V/L	0.2361	likely_benign	0.1883	benign	-0.825	Destabilizing	0.075	N	0.391	neutral	N	0.494309155	None	None	N
V/M	0.175	likely_benign	0.1387	benign	-0.712	Destabilizing	0.923	D	0.634	neutral	None	None	None	None	N
V/N	0.5949	likely_pathogenic	0.5357	ambiguous	-1.471	Destabilizing	0.987	D	0.817	deleterious	None	None	None	None	N
V/P	0.96	likely_pathogenic	0.9557	pathogenic	-1.125	Destabilizing	0.987	D	0.767	deleterious	None	None	None	None	N
V/Q	0.6405	likely_pathogenic	0.5609	ambiguous	-1.577	Destabilizing	0.987	D	0.767	deleterious	None	None	None	None	N
V/R	0.6761	likely_pathogenic	0.602	pathogenic	-1.107	Destabilizing	0.987	D	0.816	deleterious	None	None	None	None	N
V/S	0.5048	ambiguous	0.4349	ambiguous	-2.046	Highly Destabilizing	0.961	D	0.727	prob.delet.	None	None	None	None	N
V/T	0.3146	likely_benign	0.2599	benign	-1.873	Destabilizing	0.775	D	0.559	neutral	None	None	None	None	N
V/W	0.854	likely_pathogenic	0.8233	pathogenic	-1.614	Destabilizing	0.996	D	0.741	deleterious	None	None	None	None	N
V/Y	0.5753	likely_pathogenic	0.554	ambiguous	-1.312	Destabilizing	0.961	D	0.751	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.