TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5016	15271;15272;15273	chr2:178734878;178734877;178734876	chr2:179599605;179599604;179599603
N2AB	4699	14320;14321;14322	chr2:178734878;178734877;178734876	chr2:179599605;179599604;179599603
N2A	3772	11539;11540;11541	chr2:178734878;178734877;178734876	chr2:179599605;179599604;179599603
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: TTT
• RefSeq wild type template codon: AAA
• Domain: Ig-33
• Domain position: 36
• Structural Position: 49
• Q(SASA): 0.1698
• 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	rs530321856	-1.821	0.885	N	0.494	0.271	0.310147130316	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	6.47E-05	0	None	0	0	None	0	None	0	0	0
F/L	rs530321856	-1.821	0.885	N	0.494	0.271	0.310147130316	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
F/L	rs530321856	-1.821	0.885	N	0.494	0.271	0.310147130316	1000 genomes	1.99681E-04	None	None	None	None	N	None	8E-04	0	None	None	0	0	None	None	None	0	None
F/L	rs530321856	-1.821	0.885	N	0.494	0.271	0.310147130316	gnomAD-4.0.0	3.04433E-06	None	None	None	None	N	None	1.74307E-05	0	None	0	0	None	0	0	2.40984E-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	0.9532	likely_pathogenic	0.9551	pathogenic	-2.556	Highly Destabilizing	0.953	D	0.637	neutral	None	None	None	None	N
F/C	0.7628	likely_pathogenic	0.7576	pathogenic	-1.381	Destabilizing	0.999	D	0.745	deleterious	D	0.622606548	None	None	N
F/D	0.9839	likely_pathogenic	0.9781	pathogenic	-1.677	Destabilizing	0.998	D	0.783	deleterious	None	None	None	None	N
F/E	0.9688	likely_pathogenic	0.9645	pathogenic	-1.594	Destabilizing	0.993	D	0.772	deleterious	None	None	None	None	N
F/G	0.9607	likely_pathogenic	0.9607	pathogenic	-2.894	Highly Destabilizing	0.993	D	0.731	prob.delet.	None	None	None	None	N
F/H	0.6881	likely_pathogenic	0.687	pathogenic	-1.135	Destabilizing	0.986	D	0.777	deleterious	None	None	None	None	N
F/I	0.7355	likely_pathogenic	0.7501	pathogenic	-1.521	Destabilizing	0.982	D	0.649	neutral	N	0.455013348	None	None	N
F/K	0.928	likely_pathogenic	0.9108	pathogenic	-1.269	Destabilizing	0.993	D	0.774	deleterious	None	None	None	None	N
F/L	0.936	likely_pathogenic	0.9491	pathogenic	-1.521	Destabilizing	0.885	D	0.494	neutral	N	0.449250938	None	None	N
F/M	0.7878	likely_pathogenic	0.803	pathogenic	-1.221	Destabilizing	0.999	D	0.699	prob.neutral	None	None	None	None	N
F/N	0.8923	likely_pathogenic	0.8777	pathogenic	-1.267	Destabilizing	0.998	D	0.788	deleterious	None	None	None	None	N
F/P	0.9998	likely_pathogenic	0.9998	pathogenic	-1.863	Destabilizing	0.998	D	0.773	deleterious	None	None	None	None	N
F/Q	0.887	likely_pathogenic	0.886	pathogenic	-1.453	Destabilizing	0.998	D	0.777	deleterious	None	None	None	None	N
F/R	0.8454	likely_pathogenic	0.8264	pathogenic	-0.516	Destabilizing	0.993	D	0.785	deleterious	None	None	None	None	N
F/S	0.8621	likely_pathogenic	0.8596	pathogenic	-2.075	Highly Destabilizing	0.991	D	0.736	prob.delet.	N	0.459706502	None	None	N
F/T	0.9186	likely_pathogenic	0.908	pathogenic	-1.901	Destabilizing	0.993	D	0.741	deleterious	None	None	None	None	N
F/V	0.7259	likely_pathogenic	0.7415	pathogenic	-1.863	Destabilizing	0.939	D	0.621	neutral	N	0.469017388	None	None	N
F/W	0.5641	likely_pathogenic	0.5604	ambiguous	-0.59	Destabilizing	0.998	D	0.685	prob.neutral	None	None	None	None	N
F/Y	0.1201	likely_benign	0.1236	benign	-0.794	Destabilizing	0.046	N	0.313	neutral	N	0.408102633	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.