TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25406	76441;76442;76443	chr2:178569916;178569915;178569914	chr2:179434643;179434642;179434641
N2AB	23765	71518;71519;71520	chr2:178569916;178569915;178569914	chr2:179434643;179434642;179434641
N2A	22838	68737;68738;68739	chr2:178569916;178569915;178569914	chr2:179434643;179434642;179434641
N2B	16341	49246;49247;49248	chr2:178569916;178569915;178569914	chr2:179434643;179434642;179434641
Novex-1	16466	49621;49622;49623	chr2:178569916;178569915;178569914	chr2:179434643;179434642;179434641
Novex-2	16533	49822;49823;49824	chr2:178569916;178569915;178569914	chr2:179434643;179434642;179434641
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-73
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.1412
• 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
P/Q	None	None	1.0	D	0.769	0.613	0.71665822569	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.9375E-06	0	0
P/R	rs771016168	-1.219	0.999	D	0.76	0.609	0.755040375288	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.92E-06	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
P/A	0.7687	likely_pathogenic	0.82	pathogenic	-2.093	Highly Destabilizing	0.603	D	0.431	neutral	D	0.609242468	None	None	N
P/C	0.9897	likely_pathogenic	0.9923	pathogenic	-2.089	Highly Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
P/D	0.9993	likely_pathogenic	0.9995	pathogenic	-3.371	Highly Destabilizing	0.999	D	0.71	prob.delet.	None	None	None	None	N
P/E	0.9976	likely_pathogenic	0.9983	pathogenic	-3.24	Highly Destabilizing	0.999	D	0.72	deleterious	None	None	None	None	N
P/F	0.9995	likely_pathogenic	0.9996	pathogenic	-1.16	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
P/G	0.9906	likely_pathogenic	0.9937	pathogenic	-2.48	Highly Destabilizing	0.993	D	0.704	prob.delet.	None	None	None	None	N
P/H	0.9979	likely_pathogenic	0.9981	pathogenic	-1.923	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
P/I	0.9895	likely_pathogenic	0.9896	pathogenic	-1.034	Destabilizing	0.999	D	0.802	deleterious	None	None	None	None	N
P/K	0.9988	likely_pathogenic	0.9989	pathogenic	-1.782	Destabilizing	0.999	D	0.723	deleterious	None	None	None	None	N
P/L	0.9623	likely_pathogenic	0.9623	pathogenic	-1.034	Destabilizing	0.997	D	0.775	deleterious	D	0.608637055	None	None	N
P/M	0.9946	likely_pathogenic	0.9949	pathogenic	-1.302	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
P/N	0.999	likely_pathogenic	0.9992	pathogenic	-2.103	Highly Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	N
P/Q	0.9962	likely_pathogenic	0.997	pathogenic	-2.104	Highly Destabilizing	1.0	D	0.769	deleterious	D	0.647226389	None	None	N
P/R	0.9955	likely_pathogenic	0.9959	pathogenic	-1.417	Destabilizing	0.999	D	0.76	deleterious	D	0.647024585	None	None	N
P/S	0.9816	likely_pathogenic	0.9874	pathogenic	-2.513	Highly Destabilizing	0.983	D	0.666	prob.neutral	D	0.630601615	None	None	N
P/T	0.9724	likely_pathogenic	0.9781	pathogenic	-2.277	Highly Destabilizing	0.997	D	0.745	deleterious	D	0.631005224	None	None	N
P/V	0.9641	likely_pathogenic	0.9667	pathogenic	-1.364	Destabilizing	0.998	D	0.756	deleterious	None	None	None	None	N
P/W	0.9998	likely_pathogenic	0.9998	pathogenic	-1.571	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
P/Y	0.9994	likely_pathogenic	0.9995	pathogenic	-1.332	Destabilizing	1.0	D	0.836	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.