TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14119	42580;42581;42582	chr2:178634426;178634425;178634424	chr2:179499153;179499152;179499151
N2AB	12478	37657;37658;37659	chr2:178634426;178634425;178634424	chr2:179499153;179499152;179499151
N2A	11551	34876;34877;34878	chr2:178634426;178634425;178634424	chr2:179499153;179499152;179499151
N2B	5054	15385;15386;15387	chr2:178634426;178634425;178634424	chr2:179499153;179499152;179499151
Novex-1	5179	15760;15761;15762	chr2:178634426;178634425;178634424	chr2:179499153;179499152;179499151
Novex-2	5246	15961;15962;15963	chr2:178634426;178634425;178634424	chr2:179499153;179499152;179499151
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-91
• Domain position: 66
• Structural Position: 151
• Q(SASA): 0.1635
• 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	0.517	0.267	0.387202362727	gnomAD-4.0.0	1.59286E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02865E-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	0.4719	ambiguous	0.4331	ambiguous	-0.852	Destabilizing	0.999	D	0.689	prob.neutral	N	0.507530429	None	None	N
E/C	0.9846	likely_pathogenic	0.9809	pathogenic	-0.494	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
E/D	0.6303	likely_pathogenic	0.6979	pathogenic	-1.136	Destabilizing	0.999	D	0.517	neutral	N	0.514314577	None	None	N
E/F	0.9894	likely_pathogenic	0.9913	pathogenic	-0.093	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
E/G	0.6464	likely_pathogenic	0.6234	pathogenic	-1.25	Destabilizing	1.0	D	0.775	deleterious	D	0.537934516	None	None	N
E/H	0.9426	likely_pathogenic	0.9497	pathogenic	-0.312	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
E/I	0.9214	likely_pathogenic	0.9178	pathogenic	0.246	Stabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
E/K	0.597	likely_pathogenic	0.6006	pathogenic	-0.647	Destabilizing	0.999	D	0.578	neutral	D	0.605279687	None	None	N
E/L	0.9502	likely_pathogenic	0.9476	pathogenic	0.246	Stabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
E/M	0.9021	likely_pathogenic	0.8979	pathogenic	0.676	Stabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
E/N	0.8252	likely_pathogenic	0.8554	pathogenic	-1.238	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
E/P	0.9904	likely_pathogenic	0.9904	pathogenic	-0.099	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
E/Q	0.4524	ambiguous	0.4325	ambiguous	-1.063	Destabilizing	1.0	D	0.643	neutral	D	0.542432892	None	None	N
E/R	0.7862	likely_pathogenic	0.7749	pathogenic	-0.301	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	N
E/S	0.6158	likely_pathogenic	0.5929	pathogenic	-1.564	Destabilizing	0.999	D	0.613	neutral	None	None	None	None	N
E/T	0.6709	likely_pathogenic	0.7084	pathogenic	-1.226	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
E/V	0.7986	likely_pathogenic	0.8006	pathogenic	-0.099	Destabilizing	1.0	D	0.84	deleterious	D	0.537049017	None	None	N
E/W	0.9974	likely_pathogenic	0.9978	pathogenic	0.203	Stabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
E/Y	0.9818	likely_pathogenic	0.9835	pathogenic	0.175	Stabilizing	1.0	D	0.853	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.