TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26459	79600;79601;79602	chr2:178566757;178566756;178566755	chr2:179431484;179431483;179431482
N2AB	24818	74677;74678;74679	chr2:178566757;178566756;178566755	chr2:179431484;179431483;179431482
N2A	23891	71896;71897;71898	chr2:178566757;178566756;178566755	chr2:179431484;179431483;179431482
N2B	17394	52405;52406;52407	chr2:178566757;178566756;178566755	chr2:179431484;179431483;179431482
Novex-1	17519	52780;52781;52782	chr2:178566757;178566756;178566755	chr2:179431484;179431483;179431482
Novex-2	17586	52981;52982;52983	chr2:178566757;178566756;178566755	chr2:179431484;179431483;179431482
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: Fn3-80
• Domain position: 74
• Structural Position: 106
• Q(SASA): 0.0728
• 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	None	None	0.999	D	0.845	0.515	0.633181949713	gnomAD-4.0.0	2.73749E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.59813E-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	0.9987	likely_pathogenic	0.9985	pathogenic	-3.019	Highly Destabilizing	0.953	D	0.799	deleterious	None	None	None	None	N
F/C	0.9815	likely_pathogenic	0.9798	pathogenic	-1.639	Destabilizing	0.999	D	0.845	deleterious	D	0.564583674	None	None	N
F/D	0.9996	likely_pathogenic	0.9996	pathogenic	-3.912	Highly Destabilizing	0.998	D	0.874	deleterious	None	None	None	None	N
F/E	0.9997	likely_pathogenic	0.9998	pathogenic	-3.679	Highly Destabilizing	0.993	D	0.881	deleterious	None	None	None	None	N
F/G	0.9984	likely_pathogenic	0.9983	pathogenic	-3.459	Highly Destabilizing	0.993	D	0.863	deleterious	None	None	None	None	N
F/H	0.9937	likely_pathogenic	0.9945	pathogenic	-2.39	Highly Destabilizing	0.986	D	0.807	deleterious	None	None	None	None	N
F/I	0.9635	likely_pathogenic	0.9551	pathogenic	-1.545	Destabilizing	0.982	D	0.747	deleterious	N	0.50666915	None	None	N
F/K	0.9997	likely_pathogenic	0.9998	pathogenic	-2.513	Highly Destabilizing	0.993	D	0.883	deleterious	None	None	None	None	N
F/L	0.995	likely_pathogenic	0.9942	pathogenic	-1.545	Destabilizing	0.885	D	0.701	prob.neutral	N	0.511063696	None	None	N
F/M	0.9812	likely_pathogenic	0.9774	pathogenic	-1.112	Destabilizing	0.999	D	0.743	deleterious	None	None	None	None	N
F/N	0.9979	likely_pathogenic	0.9978	pathogenic	-3.218	Highly Destabilizing	0.998	D	0.89	deleterious	None	None	None	None	N
F/P	1.0	likely_pathogenic	1.0	pathogenic	-2.054	Highly Destabilizing	0.998	D	0.902	deleterious	None	None	None	None	N
F/Q	0.9996	likely_pathogenic	0.9996	pathogenic	-3.058	Highly Destabilizing	0.998	D	0.903	deleterious	None	None	None	None	N
F/R	0.9993	likely_pathogenic	0.9994	pathogenic	-2.227	Highly Destabilizing	0.993	D	0.889	deleterious	None	None	None	None	N
F/S	0.9984	likely_pathogenic	0.9983	pathogenic	-3.616	Highly Destabilizing	0.991	D	0.848	deleterious	D	0.553227369	None	None	N
F/T	0.999	likely_pathogenic	0.9989	pathogenic	-3.266	Highly Destabilizing	0.993	D	0.855	deleterious	None	None	None	None	N
F/V	0.9701	likely_pathogenic	0.9642	pathogenic	-2.054	Highly Destabilizing	0.939	D	0.756	deleterious	N	0.490522997	None	None	N
F/W	0.891	likely_pathogenic	0.9007	pathogenic	-0.81	Destabilizing	0.998	D	0.728	prob.delet.	None	None	None	None	N
F/Y	0.2455	likely_benign	0.2631	benign	-1.255	Destabilizing	0.046	N	0.245	neutral	N	0.480365822	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.