TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5077	15454;15455;15456	chr2:178734595;178734594;178734593	chr2:179599322;179599321;179599320
N2AB	4760	14503;14504;14505	chr2:178734595;178734594;178734593	chr2:179599322;179599321;179599320
N2A	3833	11722;11723;11724	chr2:178734595;178734594;178734593	chr2:179599322;179599321;179599320
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-34
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.1774
• 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	rs777568519	-1.672	0.817	D	0.537	0.637	0.536240654335	gnomAD-2.1.1	4.72E-06	None	None	None	None	N	None	0	0	None	0	5.93E-05	None	0	None	0	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	0.9811	likely_pathogenic	0.9707	pathogenic	-2.709	Highly Destabilizing	0.993	D	0.775	deleterious	None	None	None	None	N
F/C	0.9265	likely_pathogenic	0.8941	pathogenic	-1.64	Destabilizing	1.0	D	0.877	deleterious	D	0.791099572	None	None	N
F/D	0.998	likely_pathogenic	0.9977	pathogenic	-2.109	Highly Destabilizing	0.999	D	0.88	deleterious	None	None	None	None	N
F/E	0.9976	likely_pathogenic	0.9969	pathogenic	-2.035	Highly Destabilizing	0.999	D	0.876	deleterious	None	None	None	None	N
F/G	0.9952	likely_pathogenic	0.9922	pathogenic	-3.041	Highly Destabilizing	0.999	D	0.863	deleterious	None	None	None	None	N
F/H	0.9815	likely_pathogenic	0.9784	pathogenic	-1.32	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
F/I	0.5333	ambiguous	0.4373	ambiguous	-1.688	Destabilizing	0.219	N	0.315	neutral	N	0.516753199	None	None	N
F/K	0.9971	likely_pathogenic	0.9961	pathogenic	-1.471	Destabilizing	0.999	D	0.88	deleterious	None	None	None	None	N
F/L	0.9392	likely_pathogenic	0.9145	pathogenic	-1.688	Destabilizing	0.817	D	0.537	neutral	D	0.681407363	None	None	N
F/M	0.8435	likely_pathogenic	0.7838	pathogenic	-1.398	Destabilizing	0.998	D	0.728	prob.delet.	None	None	None	None	N
F/N	0.9905	likely_pathogenic	0.9882	pathogenic	-1.481	Destabilizing	0.999	D	0.892	deleterious	None	None	None	None	N
F/P	0.9953	likely_pathogenic	0.9948	pathogenic	-2.026	Highly Destabilizing	0.999	D	0.892	deleterious	None	None	None	None	N
F/Q	0.995	likely_pathogenic	0.9933	pathogenic	-1.698	Destabilizing	0.999	D	0.901	deleterious	None	None	None	None	N
F/R	0.9914	likely_pathogenic	0.9899	pathogenic	-0.671	Destabilizing	0.999	D	0.893	deleterious	None	None	None	None	N
F/S	0.9848	likely_pathogenic	0.9779	pathogenic	-2.259	Highly Destabilizing	0.999	D	0.849	deleterious	D	0.790689058	None	None	N
F/T	0.9847	likely_pathogenic	0.976	pathogenic	-2.092	Highly Destabilizing	0.993	D	0.851	deleterious	None	None	None	None	N
F/V	0.6287	likely_pathogenic	0.5156	ambiguous	-2.026	Highly Destabilizing	0.911	D	0.643	neutral	D	0.641533513	None	None	N
F/W	0.8996	likely_pathogenic	0.8912	pathogenic	-0.827	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
F/Y	0.6444	likely_pathogenic	0.6104	pathogenic	-1.008	Destabilizing	0.997	D	0.667	neutral	D	0.733559183	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.