TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8180	24763;24764;24765	chr2:178718568;178718567;178718566	chr2:179583295;179583294;179583293
N2AB	7863	23812;23813;23814	chr2:178718568;178718567;178718566	chr2:179583295;179583294;179583293
N2A	6936	21031;21032;21033	chr2:178718568;178718567;178718566	chr2:179583295;179583294;179583293
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-67
• Domain position: 10
• Structural Position: 13
• Q(SASA): 0.3577
• 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	None	N	0.239	0.286	0.549755530797	gnomAD-4.0.0	1.59299E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86203E-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	0.3837	ambiguous	0.3695	ambiguous	-1.785	Destabilizing	0.007	N	0.273	neutral	None	None	None	None	N
F/C	0.2424	likely_benign	0.2478	benign	-1.222	Destabilizing	None	N	0.273	neutral	N	0.476531471	None	None	N
F/D	0.6259	likely_pathogenic	0.6064	pathogenic	0.273	Stabilizing	0.072	N	0.434	neutral	None	None	None	None	N
F/E	0.6906	likely_pathogenic	0.6707	pathogenic	0.352	Stabilizing	0.072	N	0.404	neutral	None	None	None	None	N
F/G	0.6776	likely_pathogenic	0.6716	pathogenic	-2.095	Highly Destabilizing	0.016	N	0.377	neutral	None	None	None	None	N
F/H	0.3689	ambiguous	0.3693	ambiguous	-0.467	Destabilizing	0.628	D	0.339	neutral	None	None	None	None	N
F/I	0.128	likely_benign	0.1235	benign	-0.884	Destabilizing	0.012	N	0.217	neutral	N	0.413055995	None	None	N
F/K	0.6302	likely_pathogenic	0.6192	pathogenic	-0.973	Destabilizing	0.072	N	0.389	neutral	None	None	None	None	N
F/L	0.7297	likely_pathogenic	0.6784	pathogenic	-0.884	Destabilizing	None	N	0.067	neutral	N	0.360184303	None	None	N
F/M	0.3606	ambiguous	0.3383	benign	-0.845	Destabilizing	0.12	N	0.325	neutral	None	None	None	None	N
F/N	0.4202	ambiguous	0.4193	ambiguous	-0.997	Destabilizing	0.072	N	0.418	neutral	None	None	None	None	N
F/P	0.9862	likely_pathogenic	0.986	pathogenic	-1.173	Destabilizing	0.356	N	0.445	neutral	None	None	None	None	N
F/Q	0.5781	likely_pathogenic	0.5621	ambiguous	-0.971	Destabilizing	0.356	N	0.423	neutral	None	None	None	None	N
F/R	0.5195	ambiguous	0.5171	ambiguous	-0.479	Destabilizing	0.214	N	0.45	neutral	None	None	None	None	N
F/S	0.2646	likely_benign	0.2499	benign	-1.893	Destabilizing	None	N	0.239	neutral	N	0.441360104	None	None	N
F/T	0.2498	likely_benign	0.2146	benign	-1.717	Destabilizing	None	N	0.295	neutral	None	None	None	None	N
F/V	0.1269	likely_benign	0.1211	benign	-1.173	Destabilizing	0.012	N	0.326	neutral	N	0.392445863	None	None	N
F/W	0.5306	ambiguous	0.524	ambiguous	-0.081	Destabilizing	0.864	D	0.336	neutral	None	None	None	None	N
F/Y	0.1215	likely_benign	0.1275	benign	-0.299	Destabilizing	0.106	N	0.277	neutral	N	0.437570438	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.