TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26616	80071;80072;80073	chr2:178566286;178566285;178566284	chr2:179431013;179431012;179431011
N2AB	24975	75148;75149;75150	chr2:178566286;178566285;178566284	chr2:179431013;179431012;179431011
N2A	24048	72367;72368;72369	chr2:178566286;178566285;178566284	chr2:179431013;179431012;179431011
N2B	17551	52876;52877;52878	chr2:178566286;178566285;178566284	chr2:179431013;179431012;179431011
Novex-1	17676	53251;53252;53253	chr2:178566286;178566285;178566284	chr2:179431013;179431012;179431011
Novex-2	17743	53452;53453;53454	chr2:178566286;178566285;178566284	chr2:179431013;179431012;179431011
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-138
• Domain position: 23
• Structural Position: 35
• Q(SASA): 0.1329
• 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	rs1705818116	None	0.369	N	0.601	0.421	0.274366138417	gnomAD-4.0.0	1.20034E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07681E-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	0.9481	likely_pathogenic	0.9472	pathogenic	-2.639	Highly Destabilizing	0.916	D	0.739	prob.delet.	None	None	None	None	N
F/C	0.597	likely_pathogenic	0.554	ambiguous	-1.576	Destabilizing	0.999	D	0.767	deleterious	N	0.489251182	None	None	N
F/D	0.9985	likely_pathogenic	0.9985	pathogenic	-2.544	Highly Destabilizing	0.996	D	0.817	deleterious	None	None	None	None	N
F/E	0.9976	likely_pathogenic	0.9975	pathogenic	-2.381	Highly Destabilizing	0.996	D	0.816	deleterious	None	None	None	None	N
F/G	0.9858	likely_pathogenic	0.9868	pathogenic	-3.045	Highly Destabilizing	0.987	D	0.814	deleterious	None	None	None	None	N
F/H	0.9475	likely_pathogenic	0.9463	pathogenic	-1.374	Destabilizing	0.999	D	0.75	deleterious	None	None	None	None	N
F/I	0.4993	ambiguous	0.4611	ambiguous	-1.347	Destabilizing	0.056	N	0.393	neutral	N	0.407858032	None	None	N
F/K	0.9954	likely_pathogenic	0.9954	pathogenic	-1.987	Destabilizing	0.987	D	0.817	deleterious	None	None	None	None	N
F/L	0.966	likely_pathogenic	0.9567	pathogenic	-1.347	Destabilizing	0.369	N	0.601	neutral	N	0.497597389	None	None	N
F/M	0.8352	likely_pathogenic	0.8222	pathogenic	-0.965	Destabilizing	0.975	D	0.727	prob.delet.	None	None	None	None	N
F/N	0.9889	likely_pathogenic	0.9887	pathogenic	-2.308	Highly Destabilizing	0.996	D	0.812	deleterious	None	None	None	None	N
F/P	0.9988	likely_pathogenic	0.9989	pathogenic	-1.783	Destabilizing	0.996	D	0.815	deleterious	None	None	None	None	N
F/Q	0.9882	likely_pathogenic	0.9887	pathogenic	-2.32	Highly Destabilizing	0.999	D	0.813	deleterious	None	None	None	None	N
F/R	0.9868	likely_pathogenic	0.9867	pathogenic	-1.37	Destabilizing	0.996	D	0.818	deleterious	None	None	None	None	N
F/S	0.9454	likely_pathogenic	0.9438	pathogenic	-2.985	Highly Destabilizing	0.983	D	0.787	deleterious	D	0.528171012	None	None	N
F/T	0.9602	likely_pathogenic	0.9568	pathogenic	-2.719	Highly Destabilizing	0.975	D	0.781	deleterious	None	None	None	None	N
F/V	0.4707	ambiguous	0.4424	ambiguous	-1.783	Destabilizing	0.587	D	0.66	neutral	N	0.405233441	None	None	N
F/W	0.7648	likely_pathogenic	0.7773	pathogenic	-0.39	Destabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	N
F/Y	0.3062	likely_benign	0.3151	benign	-0.72	Destabilizing	0.944	D	0.605	neutral	N	0.515415146	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.