TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32991	99196;99197;99198	chr2:178538964;178538963;178538962	chr2:179403691;179403690;179403689
N2AB	31350	94273;94274;94275	chr2:178538964;178538963;178538962	chr2:179403691;179403690;179403689
N2A	30423	91492;91493;91494	chr2:178538964;178538963;178538962	chr2:179403691;179403690;179403689
N2B	23926	72001;72002;72003	chr2:178538964;178538963;178538962	chr2:179403691;179403690;179403689
Novex-1	24051	72376;72377;72378	chr2:178538964;178538963;178538962	chr2:179403691;179403690;179403689
Novex-2	24118	72577;72578;72579	chr2:178538964;178538963;178538962	chr2:179403691;179403690;179403689
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: Fn3-128
• Domain position: 96
• Structural Position: 129
• Q(SASA): 0.3457
• Predicted PPI site: I

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	rs1416459734	None	0.012	N	0.189	0.062	0.284150004643	gnomAD-4.0.0	3.2118E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.79153E-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	0.2289	likely_benign	0.2649	benign	-1.115	Destabilizing	0.792	D	0.434	neutral	N	0.459467784	None	None	I
V/C	0.7022	likely_pathogenic	0.7217	pathogenic	-0.738	Destabilizing	0.998	D	0.719	prob.delet.	None	None	None	None	I
V/D	0.5437	ambiguous	0.6019	pathogenic	-0.945	Destabilizing	0.988	D	0.838	deleterious	N	0.512243476	None	None	I
V/E	0.405	ambiguous	0.4467	ambiguous	-1.009	Destabilizing	0.991	D	0.791	deleterious	None	None	None	None	I
V/F	0.1696	likely_benign	0.1862	benign	-1.0	Destabilizing	0.931	D	0.683	prob.neutral	N	0.468703342	None	None	I
V/G	0.3657	ambiguous	0.4272	ambiguous	-1.355	Destabilizing	0.964	D	0.816	deleterious	N	0.467819931	None	None	I
V/H	0.5679	likely_pathogenic	0.6126	pathogenic	-0.854	Destabilizing	0.998	D	0.853	deleterious	None	None	None	None	I
V/I	0.0647	likely_benign	0.0649	benign	-0.588	Destabilizing	0.012	N	0.189	neutral	N	0.461353296	None	None	I
V/K	0.3652	ambiguous	0.3889	ambiguous	-0.989	Destabilizing	0.973	D	0.791	deleterious	None	None	None	None	I
V/L	0.1271	likely_benign	0.1419	benign	-0.588	Destabilizing	0.214	N	0.49	neutral	N	0.41844788	None	None	I
V/M	0.1426	likely_benign	0.1563	benign	-0.411	Destabilizing	0.947	D	0.717	prob.delet.	None	None	None	None	I
V/N	0.3007	likely_benign	0.3544	ambiguous	-0.681	Destabilizing	0.991	D	0.849	deleterious	None	None	None	None	I
V/P	0.5831	likely_pathogenic	0.6717	pathogenic	-0.727	Destabilizing	0.991	D	0.829	deleterious	None	None	None	None	I
V/Q	0.3484	ambiguous	0.3925	ambiguous	-0.927	Destabilizing	0.991	D	0.82	deleterious	None	None	None	None	I
V/R	0.3253	likely_benign	0.3459	ambiguous	-0.377	Destabilizing	0.991	D	0.84	deleterious	None	None	None	None	I
V/S	0.2571	likely_benign	0.3034	benign	-1.118	Destabilizing	0.973	D	0.765	deleterious	None	None	None	None	I
V/T	0.1655	likely_benign	0.181	benign	-1.081	Destabilizing	0.835	D	0.659	prob.neutral	None	None	None	None	I
V/W	0.8155	likely_pathogenic	0.8392	pathogenic	-1.115	Destabilizing	0.998	D	0.834	deleterious	None	None	None	None	I
V/Y	0.5405	ambiguous	0.5797	pathogenic	-0.849	Destabilizing	0.973	D	0.697	prob.delet.	None	None	None	None	I

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.