TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30792	92599;92600;92601	chr2:178549252;178549251;178549250	chr2:179413979;179413978;179413977
N2AB	29151	87676;87677;87678	chr2:178549252;178549251;178549250	chr2:179413979;179413978;179413977
N2A	28224	84895;84896;84897	chr2:178549252;178549251;178549250	chr2:179413979;179413978;179413977
N2B	21727	65404;65405;65406	chr2:178549252;178549251;178549250	chr2:179413979;179413978;179413977
Novex-1	21852	65779;65780;65781	chr2:178549252;178549251;178549250	chr2:179413979;179413978;179413977
Novex-2	21919	65980;65981;65982	chr2:178549252;178549251;178549250	chr2:179413979;179413978;179413977
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-112
• Domain position: 74
• Structural Position: 105
• Q(SASA): 0.0954
• 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
E/G	None	None	1.0	D	0.693	0.585	0.52297913765	gnomAD-4.0.0	1.59113E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85783E-06	0	0
E/K	rs759221234	-0.764	0.999	N	0.637	0.368	0.364926071151	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	9.94E-05	0	None	0	None	0	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
E/A	0.566	likely_pathogenic	0.5584	ambiguous	-0.69	Destabilizing	0.999	D	0.677	prob.neutral	N	0.498426716	None	None	N
E/C	0.9486	likely_pathogenic	0.9593	pathogenic	0.086	Stabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
E/D	0.8638	likely_pathogenic	0.8624	pathogenic	-1.49	Destabilizing	0.999	D	0.59	neutral	N	0.496718423	None	None	N
E/F	0.9633	likely_pathogenic	0.9724	pathogenic	-0.364	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
E/G	0.8185	likely_pathogenic	0.8089	pathogenic	-1.117	Destabilizing	1.0	D	0.693	prob.neutral	D	0.525115799	None	None	N
E/H	0.9261	likely_pathogenic	0.937	pathogenic	-0.286	Destabilizing	1.0	D	0.692	prob.neutral	None	None	None	None	N
E/I	0.7972	likely_pathogenic	0.8307	pathogenic	0.528	Stabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
E/K	0.8504	likely_pathogenic	0.8442	pathogenic	-0.502	Destabilizing	0.999	D	0.637	neutral	N	0.479384182	None	None	N
E/L	0.8705	likely_pathogenic	0.8998	pathogenic	0.528	Stabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
E/M	0.8011	likely_pathogenic	0.8441	pathogenic	1.125	Stabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
E/N	0.9295	likely_pathogenic	0.9333	pathogenic	-0.929	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
E/P	0.9984	likely_pathogenic	0.9987	pathogenic	0.139	Stabilizing	1.0	D	0.706	prob.neutral	None	None	None	None	N
E/Q	0.3168	likely_benign	0.3053	benign	-0.558	Destabilizing	1.0	D	0.687	prob.neutral	N	0.49683688	None	None	N
E/R	0.8693	likely_pathogenic	0.8746	pathogenic	-0.581	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
E/S	0.6796	likely_pathogenic	0.6825	pathogenic	-1.491	Destabilizing	0.999	D	0.666	neutral	None	None	None	None	N
E/T	0.7771	likely_pathogenic	0.7907	pathogenic	-1.066	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
E/V	0.6729	likely_pathogenic	0.7126	pathogenic	0.139	Stabilizing	1.0	D	0.669	neutral	N	0.479143919	None	None	N
E/W	0.9932	likely_pathogenic	0.9948	pathogenic	-0.537	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
E/Y	0.9501	likely_pathogenic	0.9596	pathogenic	-0.141	Destabilizing	1.0	D	0.715	prob.delet.	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.