TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8600	26023;26024;26025	chr2:178715616;178715615;178715614	chr2:179580343;179580342;179580341
N2AB	8283	25072;25073;25074	chr2:178715616;178715615;178715614	chr2:179580343;179580342;179580341
N2A	7356	22291;22292;22293	chr2:178715616;178715615;178715614	chr2:179580343;179580342;179580341
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: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Ig-71
• Domain position: 52
• Structural Position: 127
• Q(SASA): 0.392
• 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
F/L	None	None	0.97	N	0.635	0.357	0.335910606209	gnomAD-4.0.0	1.59164E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43295E-05	0
F/Y	None	None	0.989	N	0.651	0.326	0.530655398971	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
F/A	0.8965	likely_pathogenic	0.8434	pathogenic	-1.914	Destabilizing	0.583	D	0.545	neutral	None	None	None	None	N
F/C	0.8503	likely_pathogenic	0.7815	pathogenic	-1.114	Destabilizing	1.0	D	0.795	deleterious	N	0.504063754	None	None	N
F/D	0.9753	likely_pathogenic	0.9602	pathogenic	-0.212	Destabilizing	0.999	D	0.807	deleterious	None	None	None	None	N
F/E	0.9769	likely_pathogenic	0.9615	pathogenic	-0.113	Destabilizing	0.996	D	0.805	deleterious	None	None	None	None	N
F/G	0.9687	likely_pathogenic	0.9503	pathogenic	-2.249	Highly Destabilizing	0.991	D	0.743	deleterious	None	None	None	None	N
F/H	0.8643	likely_pathogenic	0.8142	pathogenic	-0.544	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
F/I	0.6245	likely_pathogenic	0.5122	ambiguous	-0.921	Destabilizing	0.985	D	0.699	prob.neutral	N	0.484794184	None	None	N
F/K	0.9757	likely_pathogenic	0.9601	pathogenic	-1.021	Destabilizing	0.997	D	0.805	deleterious	None	None	None	None	N
F/L	0.9512	likely_pathogenic	0.925	pathogenic	-0.921	Destabilizing	0.97	D	0.635	neutral	N	0.482236516	None	None	N
F/M	0.7755	likely_pathogenic	0.7088	pathogenic	-0.772	Destabilizing	0.989	D	0.741	deleterious	None	None	None	None	N
F/N	0.923	likely_pathogenic	0.8881	pathogenic	-1.096	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
F/P	0.9981	likely_pathogenic	0.9966	pathogenic	-1.243	Destabilizing	0.999	D	0.81	deleterious	None	None	None	None	N
F/Q	0.9589	likely_pathogenic	0.9364	pathogenic	-1.098	Destabilizing	0.999	D	0.808	deleterious	None	None	None	None	N
F/R	0.9391	likely_pathogenic	0.9108	pathogenic	-0.489	Destabilizing	0.997	D	0.81	deleterious	None	None	None	None	N
F/S	0.802	likely_pathogenic	0.7257	pathogenic	-1.962	Destabilizing	0.975	D	0.732	prob.delet.	N	0.512932201	None	None	N
F/T	0.8442	likely_pathogenic	0.7765	pathogenic	-1.769	Destabilizing	0.997	D	0.749	deleterious	None	None	None	None	N
F/V	0.5793	likely_pathogenic	0.472	ambiguous	-1.243	Destabilizing	0.959	D	0.706	prob.neutral	D	0.52616807	None	None	N
F/W	0.7193	likely_pathogenic	0.6681	pathogenic	-0.013	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
F/Y	0.3721	ambiguous	0.3204	benign	-0.241	Destabilizing	0.989	D	0.651	neutral	N	0.509699895	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.