TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24775	74548;74549;74550	chr2:178571809;178571808;178571807	chr2:179436536;179436535;179436534
N2AB	23134	69625;69626;69627	chr2:178571809;178571808;178571807	chr2:179436536;179436535;179436534
N2A	22207	66844;66845;66846	chr2:178571809;178571808;178571807	chr2:179436536;179436535;179436534
N2B	15710	47353;47354;47355	chr2:178571809;178571808;178571807	chr2:179436536;179436535;179436534
Novex-1	15835	47728;47729;47730	chr2:178571809;178571808;178571807	chr2:179436536;179436535;179436534
Novex-2	15902	47929;47930;47931	chr2:178571809;178571808;178571807	chr2:179436536;179436535;179436534
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-133
• Domain position: 60
• Structural Position: 140
• Q(SASA): 0.1166
• 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
I/V	rs766089174	-1.623	0.103	D	0.3	0.464	0.639007618878	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
I/V	rs766089174	-1.623	0.103	D	0.3	0.464	0.639007618878	gnomAD-4.0.0	9.58031E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.25941E-05	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
I/A	0.9655	likely_pathogenic	0.9691	pathogenic	-3.08	Highly Destabilizing	0.919	D	0.733	prob.delet.	None	None	None	None	N
I/C	0.969	likely_pathogenic	0.971	pathogenic	-2.672	Highly Destabilizing	0.999	D	0.774	deleterious	None	None	None	None	N
I/D	0.9985	likely_pathogenic	0.9989	pathogenic	-3.754	Highly Destabilizing	0.996	D	0.877	deleterious	None	None	None	None	N
I/E	0.9951	likely_pathogenic	0.996	pathogenic	-3.519	Highly Destabilizing	0.996	D	0.879	deleterious	None	None	None	None	N
I/F	0.5357	ambiguous	0.6183	pathogenic	-1.834	Destabilizing	0.976	D	0.745	deleterious	None	None	None	None	N
I/G	0.9948	likely_pathogenic	0.9956	pathogenic	-3.632	Highly Destabilizing	0.996	D	0.872	deleterious	None	None	None	None	N
I/H	0.9907	likely_pathogenic	0.9931	pathogenic	-2.993	Highly Destabilizing	0.999	D	0.861	deleterious	None	None	None	None	N
I/K	0.9881	likely_pathogenic	0.9906	pathogenic	-2.598	Highly Destabilizing	0.984	D	0.877	deleterious	D	0.649415876	None	None	N
I/L	0.2851	likely_benign	0.2938	benign	-1.459	Destabilizing	0.011	N	0.3	neutral	D	0.574930656	None	None	N
I/M	0.3156	likely_benign	0.338	benign	-1.583	Destabilizing	0.968	D	0.714	prob.delet.	D	0.594605376	None	None	N
I/N	0.9822	likely_pathogenic	0.9857	pathogenic	-3.045	Highly Destabilizing	0.996	D	0.867	deleterious	None	None	None	None	N
I/P	0.9966	likely_pathogenic	0.9972	pathogenic	-1.985	Destabilizing	0.996	D	0.873	deleterious	None	None	None	None	N
I/Q	0.9873	likely_pathogenic	0.9902	pathogenic	-2.897	Highly Destabilizing	0.996	D	0.877	deleterious	None	None	None	None	N
I/R	0.9803	likely_pathogenic	0.985	pathogenic	-2.189	Highly Destabilizing	0.984	D	0.863	deleterious	D	0.649415876	None	None	N
I/S	0.9745	likely_pathogenic	0.9779	pathogenic	-3.708	Highly Destabilizing	0.988	D	0.836	deleterious	None	None	None	None	N
I/T	0.9742	likely_pathogenic	0.9758	pathogenic	-3.33	Highly Destabilizing	0.896	D	0.777	deleterious	D	0.649012267	None	None	N
I/V	0.1227	likely_benign	0.1124	benign	-1.985	Destabilizing	0.103	N	0.3	neutral	D	0.553614032	None	None	N
I/W	0.978	likely_pathogenic	0.9842	pathogenic	-2.246	Highly Destabilizing	0.999	D	0.861	deleterious	None	None	None	None	N
I/Y	0.9534	likely_pathogenic	0.9664	pathogenic	-2.059	Highly Destabilizing	0.988	D	0.778	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.