TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6963	21112;21113;21114	chr2:178724488;178724487;178724486	chr2:179589215;179589214;179589213
N2AB	6646	20161;20162;20163	chr2:178724488;178724487;178724486	chr2:179589215;179589214;179589213
N2A	5719	17380;17381;17382	chr2:178724488;178724487;178724486	chr2:179589215;179589214;179589213
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-54
• Domain position: 16
• Structural Position: 25
• Q(SASA): 0.2704
• 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/K	None	None	0.549	N	0.356	0.231	0.199424873507	gnomAD-4.0.0	6.86362E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.02346E-07	0	0
E/Q	None	None	0.712	N	0.411	0.215	0.130388298395	gnomAD-4.0.0	6.86362E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.02346E-07	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	0.252	likely_benign	0.2476	benign	-0.468	Destabilizing	0.334	N	0.297	neutral	N	0.457608353	None	None	N
E/C	0.9152	likely_pathogenic	0.9218	pathogenic	0.008	Stabilizing	0.012	N	0.386	neutral	None	None	None	None	N
E/D	0.0817	likely_benign	0.0948	benign	-0.401	Destabilizing	0.001	N	0.159	neutral	N	0.481317562	None	None	N
E/F	0.8514	likely_pathogenic	0.8536	pathogenic	-0.327	Destabilizing	0.972	D	0.434	neutral	None	None	None	None	N
E/G	0.1804	likely_benign	0.1815	benign	-0.677	Destabilizing	0.549	D	0.371	neutral	N	0.501020831	None	None	N
E/H	0.5589	ambiguous	0.5572	ambiguous	-0.166	Destabilizing	0.972	D	0.313	neutral	None	None	None	None	N
E/I	0.7044	likely_pathogenic	0.7142	pathogenic	0.054	Stabilizing	0.92	D	0.442	neutral	None	None	None	None	N
E/K	0.2299	likely_benign	0.2262	benign	0.373	Stabilizing	0.549	D	0.356	neutral	N	0.511160467	None	None	N
E/L	0.6373	likely_pathogenic	0.6369	pathogenic	0.054	Stabilizing	0.617	D	0.417	neutral	None	None	None	None	N
E/M	0.6265	likely_pathogenic	0.6237	pathogenic	0.236	Stabilizing	0.992	D	0.413	neutral	None	None	None	None	N
E/N	0.2006	likely_benign	0.2101	benign	-0.022	Destabilizing	0.447	N	0.353	neutral	None	None	None	None	N
E/P	0.9476	likely_pathogenic	0.9554	pathogenic	-0.099	Destabilizing	0.92	D	0.339	neutral	None	None	None	None	N
E/Q	0.178	likely_benign	0.1648	benign	0.016	Stabilizing	0.712	D	0.411	neutral	N	0.486936813	None	None	N
E/R	0.3654	ambiguous	0.372	ambiguous	0.536	Stabilizing	0.92	D	0.346	neutral	None	None	None	None	N
E/S	0.2154	likely_benign	0.2187	benign	-0.169	Destabilizing	0.617	D	0.303	neutral	None	None	None	None	N
E/T	0.3733	ambiguous	0.3734	ambiguous	0.006	Stabilizing	0.617	D	0.351	neutral	None	None	None	None	N
E/V	0.4629	ambiguous	0.468	ambiguous	-0.099	Destabilizing	0.549	D	0.399	neutral	N	0.473359204	None	None	N
E/W	0.945	likely_pathogenic	0.9455	pathogenic	-0.15	Destabilizing	0.992	D	0.575	neutral	None	None	None	None	N
E/Y	0.7106	likely_pathogenic	0.7177	pathogenic	-0.071	Destabilizing	0.972	D	0.412	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.