TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17443	52552;52553;52554	chr2:178608684;178608683;178608682	chr2:179473411;179473410;179473409
N2AB	15802	47629;47630;47631	chr2:178608684;178608683;178608682	chr2:179473411;179473410;179473409
N2A	14875	44848;44849;44850	chr2:178608684;178608683;178608682	chr2:179473411;179473410;179473409
N2B	8378	25357;25358;25359	chr2:178608684;178608683;178608682	chr2:179473411;179473410;179473409
Novex-1	8503	25732;25733;25734	chr2:178608684;178608683;178608682	chr2:179473411;179473410;179473409
Novex-2	8570	25933;25934;25935	chr2:178608684;178608683;178608682	chr2:179473411;179473410;179473409
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: Fn3-14
• Domain position: 75
• Structural Position: 106
• Q(SASA): 0.0692
• 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/S	None	None	0.991	D	0.86	0.596	0.811158110691	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.9975	likely_pathogenic	0.9979	pathogenic	-1.651	Destabilizing	0.953	D	0.839	deleterious	None	None	None	None	N
F/C	0.9737	likely_pathogenic	0.9773	pathogenic	-0.56	Destabilizing	0.999	D	0.858	deleterious	D	0.541048143	None	None	N
F/D	0.9998	likely_pathogenic	0.9998	pathogenic	-2.646	Highly Destabilizing	0.998	D	0.869	deleterious	None	None	None	None	N
F/E	0.9997	likely_pathogenic	0.9998	pathogenic	-2.411	Highly Destabilizing	0.993	D	0.872	deleterious	None	None	None	None	N
F/G	0.9986	likely_pathogenic	0.9986	pathogenic	-2.075	Highly Destabilizing	0.993	D	0.867	deleterious	None	None	None	None	N
F/H	0.9964	likely_pathogenic	0.9969	pathogenic	-1.902	Destabilizing	0.986	D	0.821	deleterious	None	None	None	None	N
F/I	0.9055	likely_pathogenic	0.9178	pathogenic	-0.262	Destabilizing	0.982	D	0.73	prob.delet.	N	0.50469414	None	None	N
F/K	0.9998	likely_pathogenic	0.9998	pathogenic	-1.538	Destabilizing	0.993	D	0.871	deleterious	None	None	None	None	N
F/L	0.9729	likely_pathogenic	0.9804	pathogenic	-0.262	Destabilizing	0.885	D	0.725	prob.delet.	N	0.50365741	None	None	N
F/M	0.9523	likely_pathogenic	0.9591	pathogenic	-0.068	Destabilizing	0.999	D	0.743	deleterious	None	None	None	None	N
F/N	0.9993	likely_pathogenic	0.9994	pathogenic	-2.306	Highly Destabilizing	0.998	D	0.889	deleterious	None	None	None	None	N
F/P	0.9998	likely_pathogenic	0.9998	pathogenic	-0.738	Destabilizing	0.998	D	0.901	deleterious	None	None	None	None	N
F/Q	0.9993	likely_pathogenic	0.9994	pathogenic	-1.908	Destabilizing	0.998	D	0.902	deleterious	None	None	None	None	N
F/R	0.9991	likely_pathogenic	0.9991	pathogenic	-1.909	Destabilizing	0.993	D	0.889	deleterious	None	None	None	None	N
F/S	0.9985	likely_pathogenic	0.9986	pathogenic	-2.505	Highly Destabilizing	0.991	D	0.86	deleterious	D	0.552569032	None	None	N
F/T	0.998	likely_pathogenic	0.9982	pathogenic	-2.142	Highly Destabilizing	0.993	D	0.864	deleterious	None	None	None	None	N
F/V	0.9071	likely_pathogenic	0.918	pathogenic	-0.738	Destabilizing	0.939	D	0.801	deleterious	N	0.489535492	None	None	N
F/W	0.9337	likely_pathogenic	0.9418	pathogenic	-0.191	Destabilizing	0.998	D	0.741	deleterious	None	None	None	None	N
F/Y	0.7966	likely_pathogenic	0.8208	pathogenic	-0.5	Destabilizing	0.046	N	0.24	neutral	N	0.511801392	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.