TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18859	56800;56801;56802	chr2:178599218;178599217;178599216	chr2:179463945;179463944;179463943
N2AB	17218	51877;51878;51879	chr2:178599218;178599217;178599216	chr2:179463945;179463944;179463943
N2A	16291	49096;49097;49098	chr2:178599218;178599217;178599216	chr2:179463945;179463944;179463943
N2B	9794	29605;29606;29607	chr2:178599218;178599217;178599216	chr2:179463945;179463944;179463943
Novex-1	9919	29980;29981;29982	chr2:178599218;178599217;178599216	chr2:179463945;179463944;179463943
Novex-2	9986	30181;30182;30183	chr2:178599218;178599217;178599216	chr2:179463945;179463944;179463943
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-24
• Domain position: 76
• Structural Position: 108
• Q(SASA): 0.0594
• 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
I/V	None	None	0.003	N	0.155	0.08	0.17258766438	gnomAD-4.0.0	1.83678E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.92463E-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
I/A	0.9336	likely_pathogenic	0.9295	pathogenic	-3.207	Highly Destabilizing	0.415	N	0.615	neutral	None	None	None	None	N
I/C	0.9405	likely_pathogenic	0.9397	pathogenic	-2.542	Highly Destabilizing	0.996	D	0.743	deleterious	None	None	None	None	N
I/D	0.9991	likely_pathogenic	0.999	pathogenic	-4.031	Highly Destabilizing	0.923	D	0.835	deleterious	None	None	None	None	N
I/E	0.9971	likely_pathogenic	0.9969	pathogenic	-3.741	Highly Destabilizing	0.923	D	0.819	deleterious	None	None	None	None	N
I/F	0.7892	likely_pathogenic	0.7881	pathogenic	-2.002	Highly Destabilizing	0.901	D	0.615	neutral	N	0.506837415	None	None	N
I/G	0.9903	likely_pathogenic	0.9898	pathogenic	-3.749	Highly Destabilizing	0.858	D	0.805	deleterious	None	None	None	None	N
I/H	0.997	likely_pathogenic	0.9968	pathogenic	-3.265	Highly Destabilizing	0.989	D	0.869	deleterious	None	None	None	None	N
I/K	0.9935	likely_pathogenic	0.9935	pathogenic	-2.791	Highly Destabilizing	0.858	D	0.817	deleterious	None	None	None	None	N
I/L	0.3664	ambiguous	0.3553	ambiguous	-1.557	Destabilizing	0.19	N	0.295	neutral	N	0.502474773	None	None	N
I/M	0.4569	ambiguous	0.4317	ambiguous	-1.679	Destabilizing	0.949	D	0.635	neutral	D	0.524276984	None	None	N
I/N	0.9868	likely_pathogenic	0.9862	pathogenic	-3.445	Highly Destabilizing	0.82	D	0.849	deleterious	N	0.507597883	None	None	N
I/P	0.9956	likely_pathogenic	0.9961	pathogenic	-2.102	Highly Destabilizing	0.961	D	0.853	deleterious	None	None	None	None	N
I/Q	0.9954	likely_pathogenic	0.9952	pathogenic	-3.182	Highly Destabilizing	0.923	D	0.867	deleterious	None	None	None	None	N
I/R	0.9906	likely_pathogenic	0.99	pathogenic	-2.573	Highly Destabilizing	0.923	D	0.861	deleterious	None	None	None	None	N
I/S	0.9781	likely_pathogenic	0.976	pathogenic	-3.963	Highly Destabilizing	0.075	N	0.67	neutral	N	0.496241578	None	None	N
I/T	0.9466	likely_pathogenic	0.9444	pathogenic	-3.535	Highly Destabilizing	0.565	D	0.559	neutral	N	0.495988088	None	None	N
I/V	0.08	likely_benign	0.0823	benign	-2.102	Highly Destabilizing	0.003	N	0.155	neutral	N	0.349976725	None	None	N
I/W	0.9968	likely_pathogenic	0.9965	pathogenic	-2.413	Highly Destabilizing	0.996	D	0.842	deleterious	None	None	None	None	N
I/Y	0.9836	likely_pathogenic	0.983	pathogenic	-2.278	Highly Destabilizing	0.961	D	0.706	prob.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.