TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7020	21283;21284;21285	chr2:178724317;178724316;178724315	chr2:179589044;179589043;179589042
N2AB	6703	20332;20333;20334	chr2:178724317;178724316;178724315	chr2:179589044;179589043;179589042
N2A	5776	17551;17552;17553	chr2:178724317;178724316;178724315	chr2:179589044;179589043;179589042
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-54
• Domain position: 73
• Structural Position: 156
• Q(SASA): 0.0616
• 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	None	None	0.989	N	0.685	0.289	0.26547132957	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-05	0
F/S	rs1377671005	None	0.998	N	0.805	0.432	0.673376435606	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	1.92901E-04	None	0	0	0	0	0
F/S	rs1377671005	None	0.998	N	0.805	0.432	0.673376435606	gnomAD-4.0.0	6.08958E-06	None	None	None	None	N	None	0	0	None	0	1.13456E-04	None	0	0	6.02472E-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	0.9727	likely_pathogenic	0.9807	pathogenic	-2.756	Highly Destabilizing	0.992	D	0.785	deleterious	None	None	None	None	N
F/C	0.7232	likely_pathogenic	0.8027	pathogenic	-1.497	Destabilizing	0.391	N	0.693	prob.neutral	N	0.251396093	None	None	N
F/D	0.9997	likely_pathogenic	0.9998	pathogenic	-3.004	Highly Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
F/E	0.9993	likely_pathogenic	0.9996	pathogenic	-2.806	Highly Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
F/G	0.9918	likely_pathogenic	0.9951	pathogenic	-3.181	Highly Destabilizing	0.999	D	0.831	deleterious	None	None	None	None	N
F/H	0.993	likely_pathogenic	0.9952	pathogenic	-1.704	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
F/I	0.7017	likely_pathogenic	0.7085	pathogenic	-1.372	Destabilizing	0.994	D	0.704	prob.neutral	N	0.409953322	None	None	N
F/K	0.9993	likely_pathogenic	0.9995	pathogenic	-1.744	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
F/L	0.9549	likely_pathogenic	0.9602	pathogenic	-1.372	Destabilizing	0.989	D	0.685	prob.neutral	N	0.341458816	None	None	N
F/M	0.8758	likely_pathogenic	0.8989	pathogenic	-1.066	Destabilizing	1.0	D	0.682	prob.neutral	None	None	None	None	N
F/N	0.9971	likely_pathogenic	0.9984	pathogenic	-2.189	Highly Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
F/P	0.9998	likely_pathogenic	0.9998	pathogenic	-1.844	Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
F/Q	0.9979	likely_pathogenic	0.9986	pathogenic	-2.164	Highly Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
F/R	0.9964	likely_pathogenic	0.9975	pathogenic	-1.284	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
F/S	0.9887	likely_pathogenic	0.9918	pathogenic	-2.813	Highly Destabilizing	0.998	D	0.805	deleterious	N	0.444530043	None	None	N
F/T	0.9908	likely_pathogenic	0.9935	pathogenic	-2.508	Highly Destabilizing	0.999	D	0.808	deleterious	None	None	None	None	N
F/V	0.6223	likely_pathogenic	0.6485	pathogenic	-1.844	Destabilizing	0.989	D	0.737	prob.delet.	N	0.386633745	None	None	N
F/W	0.9671	likely_pathogenic	0.9683	pathogenic	-0.351	Destabilizing	1.0	D	0.653	neutral	None	None	None	None	N
F/Y	0.6682	likely_pathogenic	0.7271	pathogenic	-0.719	Destabilizing	0.998	D	0.623	neutral	N	0.474159516	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.