TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29671	89236;89237;89238	chr2:178554100;178554099;178554098	chr2:179418827;179418826;179418825
N2AB	28030	84313;84314;84315	chr2:178554100;178554099;178554098	chr2:179418827;179418826;179418825
N2A	27103	81532;81533;81534	chr2:178554100;178554099;178554098	chr2:179418827;179418826;179418825
N2B	20606	62041;62042;62043	chr2:178554100;178554099;178554098	chr2:179418827;179418826;179418825
Novex-1	20731	62416;62417;62418	chr2:178554100;178554099;178554098	chr2:179418827;179418826;179418825
Novex-2	20798	62617;62618;62619	chr2:178554100;178554099;178554098	chr2:179418827;179418826;179418825
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: Fn3-104
• Domain position: 39
• Structural Position: 41
• Q(SASA): 0.1176
• 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/Q	None	None	1.0	N	0.77	0.304	0.279370189704	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05

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	0.8331	likely_pathogenic	0.8805	pathogenic	-0.284	Destabilizing	0.999	D	0.704	prob.neutral	D	0.537660193	None	None	N
E/C	0.981	likely_pathogenic	0.983	pathogenic	0.221	Stabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
E/D	0.6827	likely_pathogenic	0.739	pathogenic	-1.727	Destabilizing	0.999	D	0.667	neutral	N	0.478498809	None	None	N
E/F	0.9788	likely_pathogenic	0.981	pathogenic	-0.118	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
E/G	0.8774	likely_pathogenic	0.9175	pathogenic	-0.658	Destabilizing	1.0	D	0.748	deleterious	N	0.521330364	None	None	N
E/H	0.9418	likely_pathogenic	0.9553	pathogenic	-0.064	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
E/I	0.951	likely_pathogenic	0.962	pathogenic	0.77	Stabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
E/K	0.9029	likely_pathogenic	0.9402	pathogenic	-0.404	Destabilizing	0.999	D	0.711	prob.delet.	N	0.51154054	None	None	N
E/L	0.9129	likely_pathogenic	0.9287	pathogenic	0.77	Stabilizing	1.0	D	0.768	deleterious	None	None	None	None	N
E/M	0.9123	likely_pathogenic	0.9266	pathogenic	1.189	Stabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
E/N	0.9389	likely_pathogenic	0.9584	pathogenic	-0.837	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
E/P	0.9991	likely_pathogenic	0.9994	pathogenic	0.435	Stabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
E/Q	0.4403	ambiguous	0.5435	ambiguous	-0.494	Destabilizing	1.0	D	0.77	deleterious	N	0.474166715	None	None	N
E/R	0.9331	likely_pathogenic	0.9558	pathogenic	-0.537	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
E/S	0.8564	likely_pathogenic	0.899	pathogenic	-1.218	Destabilizing	0.999	D	0.759	deleterious	None	None	None	None	N
E/T	0.9355	likely_pathogenic	0.9532	pathogenic	-0.849	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
E/V	0.8724	likely_pathogenic	0.8967	pathogenic	0.435	Stabilizing	1.0	D	0.744	deleterious	D	0.531672712	None	None	N
E/W	0.9908	likely_pathogenic	0.9923	pathogenic	-0.436	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
E/Y	0.9634	likely_pathogenic	0.9686	pathogenic	0.047	Stabilizing	1.0	D	0.779	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.