TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14855	44788;44789;44790	chr2:178624717;178624716;178624715	chr2:179489444;179489443;179489442
N2AB	13214	39865;39866;39867	chr2:178624717;178624716;178624715	chr2:179489444;179489443;179489442
N2A	12287	37084;37085;37086	chr2:178624717;178624716;178624715	chr2:179489444;179489443;179489442
N2B	5790	17593;17594;17595	chr2:178624717;178624716;178624715	chr2:179489444;179489443;179489442
Novex-1	5915	17968;17969;17970	chr2:178624717;178624716;178624715	chr2:179489444;179489443;179489442
Novex-2	5982	18169;18170;18171	chr2:178624717;178624716;178624715	chr2:179489444;179489443;179489442
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-100
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.1036
• 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	rs1424075362	-2.721	0.369	D	0.605	0.613	0.382592752248	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.95E-06	0
F/L	rs1424075362	-2.721	0.369	D	0.605	0.613	0.382592752248	gnomAD-4.0.0	1.59464E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86449E-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	0.997	likely_pathogenic	0.9964	pathogenic	-2.785	Highly Destabilizing	0.916	D	0.788	deleterious	None	None	None	None	N
F/C	0.9899	likely_pathogenic	0.99	pathogenic	-1.535	Destabilizing	0.999	D	0.843	deleterious	D	0.766846404	None	None	N
F/D	0.9984	likely_pathogenic	0.998	pathogenic	-2.528	Highly Destabilizing	0.996	D	0.865	deleterious	None	None	None	None	N
F/E	0.9986	likely_pathogenic	0.9984	pathogenic	-2.426	Highly Destabilizing	0.996	D	0.868	deleterious	None	None	None	None	N
F/G	0.9981	likely_pathogenic	0.998	pathogenic	-3.143	Highly Destabilizing	0.987	D	0.859	deleterious	None	None	None	None	N
F/H	0.9958	likely_pathogenic	0.9955	pathogenic	-1.46	Destabilizing	0.999	D	0.781	deleterious	None	None	None	None	N
F/I	0.8783	likely_pathogenic	0.8526	pathogenic	-1.658	Destabilizing	0.056	N	0.415	neutral	N	0.510147617	None	None	N
F/K	0.9989	likely_pathogenic	0.9987	pathogenic	-1.499	Destabilizing	0.987	D	0.866	deleterious	None	None	None	None	N
F/L	0.9968	likely_pathogenic	0.9966	pathogenic	-1.658	Destabilizing	0.369	N	0.605	neutral	D	0.634312494	None	None	N
F/M	0.9683	likely_pathogenic	0.9642	pathogenic	-1.339	Destabilizing	0.975	D	0.746	deleterious	None	None	None	None	N
F/N	0.9955	likely_pathogenic	0.9947	pathogenic	-1.602	Destabilizing	0.996	D	0.869	deleterious	None	None	None	None	N
F/P	0.9997	likely_pathogenic	0.9995	pathogenic	-2.036	Highly Destabilizing	0.996	D	0.871	deleterious	None	None	None	None	N
F/Q	0.9987	likely_pathogenic	0.9986	pathogenic	-1.77	Destabilizing	0.999	D	0.87	deleterious	None	None	None	None	N
F/R	0.9978	likely_pathogenic	0.9974	pathogenic	-0.758	Destabilizing	0.996	D	0.875	deleterious	None	None	None	None	N
F/S	0.9978	likely_pathogenic	0.9976	pathogenic	-2.314	Highly Destabilizing	0.983	D	0.843	deleterious	D	0.801347206	None	None	N
F/T	0.9971	likely_pathogenic	0.9969	pathogenic	-2.118	Highly Destabilizing	0.975	D	0.838	deleterious	None	None	None	None	N
F/V	0.9248	likely_pathogenic	0.9148	pathogenic	-2.036	Highly Destabilizing	0.587	D	0.681	prob.neutral	D	0.629873297	None	None	N
F/W	0.9665	likely_pathogenic	0.9613	pathogenic	-0.644	Destabilizing	0.999	D	0.727	prob.delet.	None	None	None	None	N
F/Y	0.8042	likely_pathogenic	0.7843	pathogenic	-0.918	Destabilizing	0.944	D	0.59	neutral	D	0.766497535	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.