TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24045	72358;72359;72360	chr2:178573999;178573998;178573997	chr2:179438726;179438725;179438724
N2AB	22404	67435;67436;67437	chr2:178573999;178573998;178573997	chr2:179438726;179438725;179438724
N2A	21477	64654;64655;64656	chr2:178573999;178573998;178573997	chr2:179438726;179438725;179438724
N2B	14980	45163;45164;45165	chr2:178573999;178573998;178573997	chr2:179438726;179438725;179438724
Novex-1	15105	45538;45539;45540	chr2:178573999;178573998;178573997	chr2:179438726;179438725;179438724
Novex-2	15172	45739;45740;45741	chr2:178573999;178573998;178573997	chr2:179438726;179438725;179438724
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-131
• Domain position: 17
• Structural Position: 25
• Q(SASA): 0.3685
• 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	rs1406753487	0.307	0.892	N	0.497	0.274	0.288352970974	gnomAD-2.1.1	8.06E-06	None	None	None	None	N	None	0	0	None	0	0	None	6.54E-05	None	0	0	0
E/K	rs1406753487	0.307	0.892	N	0.497	0.274	0.288352970974	gnomAD-4.0.0	2.73756E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.31911E-05	3.31433E-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	0.2257	likely_benign	0.273	benign	-0.703	Destabilizing	0.892	D	0.545	neutral	N	0.466002144	None	None	N
E/C	0.881	likely_pathogenic	0.9004	pathogenic	-0.188	Destabilizing	0.999	D	0.771	deleterious	None	None	None	None	N
E/D	0.1188	likely_benign	0.1275	benign	-0.57	Destabilizing	0.011	N	0.218	neutral	N	0.467580261	None	None	N
E/F	0.8389	likely_pathogenic	0.8742	pathogenic	-0.358	Destabilizing	0.999	D	0.752	deleterious	None	None	None	None	N
E/G	0.2376	likely_benign	0.2748	benign	-0.961	Destabilizing	0.892	D	0.568	neutral	N	0.496172371	None	None	N
E/H	0.5824	likely_pathogenic	0.6317	pathogenic	-0.278	Destabilizing	0.999	D	0.603	neutral	None	None	None	None	N
E/I	0.5556	ambiguous	0.6357	pathogenic	-0.031	Destabilizing	0.987	D	0.768	deleterious	None	None	None	None	N
E/K	0.2075	likely_benign	0.2484	benign	0.167	Stabilizing	0.892	D	0.497	neutral	N	0.461113845	None	None	N
E/L	0.5566	ambiguous	0.629	pathogenic	-0.031	Destabilizing	0.987	D	0.753	deleterious	None	None	None	None	N
E/M	0.5481	ambiguous	0.6202	pathogenic	0.222	Stabilizing	0.999	D	0.705	prob.neutral	None	None	None	None	N
E/N	0.2952	likely_benign	0.3454	ambiguous	-0.362	Destabilizing	0.95	D	0.592	neutral	None	None	None	None	N
E/P	0.9657	likely_pathogenic	0.9668	pathogenic	-0.235	Destabilizing	0.987	D	0.653	neutral	None	None	None	None	N
E/Q	0.1836	likely_benign	0.2098	benign	-0.291	Destabilizing	0.983	D	0.599	neutral	N	0.512256545	None	None	N
E/R	0.3904	ambiguous	0.4363	ambiguous	0.391	Stabilizing	0.987	D	0.628	neutral	None	None	None	None	N
E/S	0.2526	likely_benign	0.2962	benign	-0.534	Destabilizing	0.916	D	0.501	neutral	None	None	None	None	N
E/T	0.3126	likely_benign	0.356	ambiguous	-0.309	Destabilizing	0.975	D	0.607	neutral	None	None	None	None	N
E/V	0.3266	likely_benign	0.3903	ambiguous	-0.235	Destabilizing	0.983	D	0.703	prob.neutral	N	0.476815471	None	None	N
E/W	0.9463	likely_pathogenic	0.9571	pathogenic	-0.09	Destabilizing	0.999	D	0.771	deleterious	None	None	None	None	N
E/Y	0.7162	likely_pathogenic	0.7676	pathogenic	-0.082	Destabilizing	0.999	D	0.711	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.