TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19005	57238;57239;57240	chr2:178598604;178598603;178598602	chr2:179463331;179463330;179463329
N2AB	17364	52315;52316;52317	chr2:178598604;178598603;178598602	chr2:179463331;179463330;179463329
N2A	16437	49534;49535;49536	chr2:178598604;178598603;178598602	chr2:179463331;179463330;179463329
N2B	9940	30043;30044;30045	chr2:178598604;178598603;178598602	chr2:179463331;179463330;179463329
Novex-1	10065	30418;30419;30420	chr2:178598604;178598603;178598602	chr2:179463331;179463330;179463329
Novex-2	10132	30619;30620;30621	chr2:178598604;178598603;178598602	chr2:179463331;179463330;179463329
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Fn3-26
• Domain position: 18
• Structural Position: 20
• Q(SASA): 0.1313
• 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
A/V	None	None	None	N	0.247	0.089	0.0551355673512	gnomAD-4.0.0	2.40065E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.62501E-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
A/C	0.4514	ambiguous	0.4675	ambiguous	-1.571	Destabilizing	0.824	D	0.681	prob.neutral	None	None	None	None	N
A/D	0.9908	likely_pathogenic	0.9902	pathogenic	-2.207	Highly Destabilizing	0.555	D	0.79	deleterious	None	None	None	None	N
A/E	0.9773	likely_pathogenic	0.975	pathogenic	-1.974	Destabilizing	0.211	N	0.783	deleterious	N	0.474696466	None	None	N
A/F	0.8601	likely_pathogenic	0.8635	pathogenic	-0.729	Destabilizing	0.38	N	0.796	deleterious	None	None	None	None	N
A/G	0.4634	ambiguous	0.4392	ambiguous	-1.594	Destabilizing	0.211	N	0.616	neutral	N	0.468113101	None	None	N
A/H	0.9892	likely_pathogenic	0.9885	pathogenic	-2.081	Highly Destabilizing	0.935	D	0.763	deleterious	None	None	None	None	N
A/I	0.1489	likely_benign	0.165	benign	0.369	Stabilizing	0.012	N	0.609	neutral	None	None	None	None	N
A/K	0.9907	likely_pathogenic	0.988	pathogenic	-1.163	Destabilizing	0.262	N	0.793	deleterious	None	None	None	None	N
A/L	0.3207	likely_benign	0.3247	benign	0.369	Stabilizing	0.035	N	0.587	neutral	None	None	None	None	N
A/M	0.4275	ambiguous	0.4465	ambiguous	-0.16	Destabilizing	0.38	N	0.781	deleterious	None	None	None	None	N
A/N	0.9619	likely_pathogenic	0.9619	pathogenic	-1.579	Destabilizing	0.791	D	0.797	deleterious	None	None	None	None	N
A/P	0.9776	likely_pathogenic	0.9775	pathogenic	-0.064	Destabilizing	0.484	N	0.813	deleterious	N	0.486052772	None	None	N
A/Q	0.9639	likely_pathogenic	0.9607	pathogenic	-1.309	Destabilizing	0.791	D	0.811	deleterious	None	None	None	None	N
A/R	0.9749	likely_pathogenic	0.9693	pathogenic	-1.397	Destabilizing	0.555	D	0.813	deleterious	None	None	None	None	N
A/S	0.341	ambiguous	0.3515	ambiguous	-2.071	Highly Destabilizing	0.117	N	0.621	neutral	N	0.51622793	None	None	N
A/T	0.1698	likely_benign	0.1838	benign	-1.68	Destabilizing	0.062	N	0.599	neutral	N	0.474189487	None	None	N
A/V	0.054	likely_benign	0.0608	benign	-0.064	Destabilizing	None	N	0.247	neutral	N	0.356604414	None	None	N
A/W	0.993	likely_pathogenic	0.9924	pathogenic	-1.473	Destabilizing	0.935	D	0.783	deleterious	None	None	None	None	N
A/Y	0.9737	likely_pathogenic	0.9718	pathogenic	-0.887	Destabilizing	0.555	D	0.799	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.