TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5348	16267;16268;16269	chr2:178733251;178733250;178733249	chr2:179597978;179597977;179597976
N2AB	5031	15316;15317;15318	chr2:178733251;178733250;178733249	chr2:179597978;179597977;179597976
N2A	4104	12535;12536;12537	chr2:178733251;178733250;178733249	chr2:179597978;179597977;179597976
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-36
• Domain position: 88
• Structural Position: 174
• Q(SASA): 0.1605
• 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/C	rs766802878	-2.203	0.978	N	0.761	0.41	0.652953024311	gnomAD-2.1.1	4.23E-06	None	None	None	None	N	None	0	0	None	0	5.58E-05	None	0	None	0	0	0
F/C	rs766802878	-2.203	0.978	N	0.761	0.41	0.652953024311	gnomAD-4.0.0	3.24993E-06	None	None	None	None	N	None	0	0	None	0	2.77886E-05	None	0	0	0	1.49254E-05	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	0.9539	likely_pathogenic	0.9376	pathogenic	-2.186	Highly Destabilizing	0.228	N	0.582	neutral	None	None	None	None	N
F/C	0.7769	likely_pathogenic	0.6645	pathogenic	-1.4	Destabilizing	0.978	D	0.761	deleterious	N	0.46186501	None	None	N
F/D	0.9975	likely_pathogenic	0.9971	pathogenic	-2.944	Highly Destabilizing	0.94	D	0.769	deleterious	None	None	None	None	N
F/E	0.9955	likely_pathogenic	0.9952	pathogenic	-2.692	Highly Destabilizing	0.836	D	0.767	deleterious	None	None	None	None	N
F/G	0.9888	likely_pathogenic	0.9852	pathogenic	-2.672	Highly Destabilizing	0.593	D	0.737	prob.delet.	None	None	None	None	N
F/H	0.982	likely_pathogenic	0.978	pathogenic	-1.768	Destabilizing	0.983	D	0.729	prob.delet.	None	None	None	None	N
F/I	0.3186	likely_benign	0.2247	benign	-0.601	Destabilizing	0.003	N	0.331	neutral	N	0.35558012	None	None	N
F/K	0.9954	likely_pathogenic	0.9951	pathogenic	-1.704	Destabilizing	0.836	D	0.757	deleterious	None	None	None	None	N
F/L	0.7595	likely_pathogenic	0.6836	pathogenic	-0.601	Destabilizing	None	N	0.307	neutral	N	0.23082882	None	None	N
F/M	0.6445	likely_pathogenic	0.5581	ambiguous	-0.508	Destabilizing	0.716	D	0.656	neutral	None	None	None	None	N
F/N	0.9908	likely_pathogenic	0.9887	pathogenic	-2.372	Highly Destabilizing	0.94	D	0.778	deleterious	None	None	None	None	N
F/P	0.9986	likely_pathogenic	0.9981	pathogenic	-1.142	Destabilizing	0.94	D	0.778	deleterious	None	None	None	None	N
F/Q	0.9919	likely_pathogenic	0.9909	pathogenic	-2.141	Highly Destabilizing	0.94	D	0.788	deleterious	None	None	None	None	N
F/R	0.9877	likely_pathogenic	0.9877	pathogenic	-1.655	Destabilizing	0.836	D	0.772	deleterious	None	None	None	None	N
F/S	0.9793	likely_pathogenic	0.9706	pathogenic	-2.896	Highly Destabilizing	0.523	D	0.698	prob.neutral	N	0.462038368	None	None	N
F/T	0.9705	likely_pathogenic	0.9562	pathogenic	-2.51	Highly Destabilizing	0.418	N	0.667	neutral	None	None	None	None	N
F/V	0.3385	likely_benign	0.2486	benign	-1.142	Destabilizing	0.003	N	0.401	neutral	N	0.272286733	None	None	N
F/W	0.8695	likely_pathogenic	0.8416	pathogenic	-0.054	Destabilizing	0.983	D	0.639	neutral	None	None	None	None	N
F/Y	0.5392	ambiguous	0.497	ambiguous	-0.402	Destabilizing	0.523	D	0.589	neutral	N	0.46186501	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.