TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	958	3097;3098;3099	chr2:178783034;178783033;178783032	chr2:179647761;179647760;179647759
N2AB	958	3097;3098;3099	chr2:178783034;178783033;178783032	chr2:179647761;179647760;179647759
N2A	958	3097;3098;3099	chr2:178783034;178783033;178783032	chr2:179647761;179647760;179647759
N2B	912	2959;2960;2961	chr2:178783034;178783033;178783032	chr2:179647761;179647760;179647759
Novex-1	912	2959;2960;2961	chr2:178783034;178783033;178783032	chr2:179647761;179647760;179647759
Novex-2	912	2959;2960;2961	chr2:178783034;178783033;178783032	chr2:179647761;179647760;179647759
Novex-3	958	3097;3098;3099	chr2:178783034;178783033;178783032	chr2:179647761;179647760;179647759

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-3
• Domain position: 16
• Structural Position: 25
• Q(SASA): 0.327
• 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/D	None	None	0.999	N	0.413	0.368	0.315903272564	gnomAD-4.0.0	1.20037E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31256E-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
E/A	0.523	ambiguous	0.5897	pathogenic	-0.606	Destabilizing	0.999	D	0.592	neutral	N	0.520170505	None	None	N
E/C	0.9901	likely_pathogenic	0.9918	pathogenic	-0.153	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
E/D	0.4275	ambiguous	0.4614	ambiguous	-0.538	Destabilizing	0.999	D	0.413	neutral	N	0.499633631	None	None	N
E/F	0.9836	likely_pathogenic	0.9866	pathogenic	-0.305	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
E/G	0.5619	ambiguous	0.6153	pathogenic	-0.85	Destabilizing	1.0	D	0.649	neutral	N	0.510911998	None	None	N
E/H	0.909	likely_pathogenic	0.9269	pathogenic	-0.187	Destabilizing	1.0	D	0.644	neutral	None	None	None	None	N
E/I	0.9345	likely_pathogenic	0.9516	pathogenic	0.023	Stabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
E/K	0.4741	ambiguous	0.5561	ambiguous	0.209	Stabilizing	0.999	D	0.537	neutral	D	0.524110528	None	None	N
E/L	0.9237	likely_pathogenic	0.9422	pathogenic	0.023	Stabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
E/M	0.8867	likely_pathogenic	0.9116	pathogenic	0.213	Stabilizing	1.0	D	0.669	neutral	None	None	None	None	N
E/N	0.654	likely_pathogenic	0.7069	pathogenic	-0.291	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	N
E/P	0.9981	likely_pathogenic	0.9985	pathogenic	-0.166	Destabilizing	1.0	D	0.654	neutral	None	None	None	None	N
E/Q	0.297	likely_benign	0.3417	ambiguous	-0.227	Destabilizing	1.0	D	0.601	neutral	N	0.491746322	None	None	N
E/R	0.6871	likely_pathogenic	0.7492	pathogenic	0.431	Stabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
E/S	0.5457	ambiguous	0.6029	pathogenic	-0.442	Destabilizing	0.999	D	0.618	neutral	None	None	None	None	N
E/T	0.7328	likely_pathogenic	0.7904	pathogenic	-0.234	Destabilizing	1.0	D	0.673	neutral	None	None	None	None	N
E/V	0.8084	likely_pathogenic	0.85	pathogenic	-0.166	Destabilizing	1.0	D	0.696	prob.neutral	D	0.611169683	None	None	N
E/W	0.9967	likely_pathogenic	0.9973	pathogenic	-0.067	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
E/Y	0.9696	likely_pathogenic	0.9758	pathogenic	-0.039	Destabilizing	1.0	D	0.698	prob.neutral	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.