TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33626	101101;101102;101103	chr2:178535739;178535738;178535737	chr2:179400466;179400465;179400464
N2AB	31985	96178;96179;96180	chr2:178535739;178535738;178535737	chr2:179400466;179400465;179400464
N2A	31058	93397;93398;93399	chr2:178535739;178535738;178535737	chr2:179400466;179400465;179400464
N2B	24561	73906;73907;73908	chr2:178535739;178535738;178535737	chr2:179400466;179400465;179400464
Novex-1	24686	74281;74282;74283	chr2:178535739;178535738;178535737	chr2:179400466;179400465;179400464
Novex-2	24753	74482;74483;74484	chr2:178535739;178535738;178535737	chr2:179400466;179400465;179400464
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-159
• Domain position: 31
• Structural Position: 45
• Q(SASA): 0.4855
• 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/M	rs1222398324	None	0.999	N	0.588	0.276	0.525561869914	gnomAD-3.1.2	1.97E-05	None	None	None	None	I	None	0	0	0	0	0	None	0	0	4.41E-05	0	0
V/M	rs1222398324	None	0.999	N	0.588	0.276	0.525561869914	gnomAD-4.0.0	1.48744E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.03427E-05	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	0.6329	likely_pathogenic	0.3833	ambiguous	-0.748	Destabilizing	0.271	N	0.216	neutral	N	0.474856603	None	None	I
V/C	0.9566	likely_pathogenic	0.9278	pathogenic	-0.618	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	I
V/D	0.9256	likely_pathogenic	0.7984	pathogenic	-0.795	Destabilizing	0.999	D	0.782	deleterious	None	None	None	None	I
V/E	0.8395	likely_pathogenic	0.6453	pathogenic	-0.885	Destabilizing	0.995	D	0.719	prob.delet.	N	0.462001949	None	None	I
V/F	0.643	likely_pathogenic	0.4327	ambiguous	-0.841	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	I
V/G	0.8235	likely_pathogenic	0.6566	pathogenic	-0.928	Destabilizing	0.995	D	0.676	prob.neutral	N	0.490808118	None	None	I
V/H	0.9474	likely_pathogenic	0.8706	pathogenic	-0.505	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	I
V/I	0.1191	likely_benign	0.0975	benign	-0.402	Destabilizing	0.919	D	0.462	neutral	None	None	None	None	I
V/K	0.9068	likely_pathogenic	0.7763	pathogenic	-0.769	Destabilizing	0.998	D	0.741	deleterious	None	None	None	None	I
V/L	0.5106	ambiguous	0.334	benign	-0.402	Destabilizing	0.809	D	0.46	neutral	N	0.520802323	None	None	I
V/M	0.4334	ambiguous	0.2421	benign	-0.392	Destabilizing	0.999	D	0.588	neutral	N	0.502835987	None	None	I
V/N	0.7608	likely_pathogenic	0.5415	ambiguous	-0.473	Destabilizing	0.996	D	0.788	deleterious	None	None	None	None	I
V/P	0.9856	likely_pathogenic	0.9725	pathogenic	-0.482	Destabilizing	0.988	D	0.777	deleterious	None	None	None	None	I
V/Q	0.8059	likely_pathogenic	0.617	pathogenic	-0.721	Destabilizing	0.999	D	0.783	deleterious	None	None	None	None	I
V/R	0.8883	likely_pathogenic	0.7712	pathogenic	-0.191	Destabilizing	0.999	D	0.787	deleterious	None	None	None	None	I
V/S	0.6852	likely_pathogenic	0.4505	ambiguous	-0.799	Destabilizing	0.978	D	0.637	neutral	None	None	None	None	I
V/T	0.5679	likely_pathogenic	0.3513	ambiguous	-0.792	Destabilizing	0.972	D	0.483	neutral	None	None	None	None	I
V/W	0.991	likely_pathogenic	0.9798	pathogenic	-0.958	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	I
V/Y	0.9335	likely_pathogenic	0.8682	pathogenic	-0.67	Destabilizing	1.0	D	0.751	deleterious	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.