TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6463	19612;19613;19614	chr2:178728539;178728538;178728537	chr2:179593266;179593265;179593264
N2AB	6146	18661;18662;18663	chr2:178728539;178728538;178728537	chr2:179593266;179593265;179593264
N2A	5219	15880;15881;15882	chr2:178728539;178728538;178728537	chr2:179593266;179593265;179593264
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-48
• Domain position: 79
• Structural Position: 163
• Q(SASA): 0.9011
• Predicted PPI site: I

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	rs267599062	-0.092	0.704	N	0.296	0.197	0.265010934533	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
F/L	rs267599062	-0.092	0.704	N	0.296	0.197	0.265010934533	gnomAD-4.0.0	1.23278E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.53022E-05	0	1.65843E-05

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	0.5036	ambiguous	0.5307	ambiguous	-0.53	Destabilizing	0.863	D	0.538	neutral	None	None	None	None	I
F/C	0.3713	ambiguous	0.4017	ambiguous	-0.126	Destabilizing	0.999	D	0.591	neutral	N	0.51528186	None	None	I
F/D	0.8718	likely_pathogenic	0.9004	pathogenic	0.906	Stabilizing	0.991	D	0.565	neutral	None	None	None	None	I
F/E	0.9007	likely_pathogenic	0.9219	pathogenic	0.861	Stabilizing	0.997	D	0.568	neutral	None	None	None	None	I
F/G	0.8533	likely_pathogenic	0.8683	pathogenic	-0.675	Destabilizing	0.02	N	0.387	neutral	None	None	None	None	I
F/H	0.5848	likely_pathogenic	0.6575	pathogenic	0.397	Stabilizing	0.999	D	0.539	neutral	None	None	None	None	I
F/I	0.1997	likely_benign	0.2409	benign	-0.197	Destabilizing	0.061	N	0.223	neutral	N	0.42348642	None	None	I
F/K	0.8882	likely_pathogenic	0.9157	pathogenic	0.216	Stabilizing	0.991	D	0.57	neutral	None	None	None	None	I
F/L	0.8749	likely_pathogenic	0.8895	pathogenic	-0.197	Destabilizing	0.704	D	0.296	neutral	N	0.444168336	None	None	I
F/M	0.6078	likely_pathogenic	0.6379	pathogenic	-0.184	Destabilizing	0.991	D	0.443	neutral	None	None	None	None	I
F/N	0.7623	likely_pathogenic	0.7935	pathogenic	0.281	Stabilizing	0.991	D	0.576	neutral	None	None	None	None	I
F/P	0.9952	likely_pathogenic	0.9953	pathogenic	-0.288	Destabilizing	0.997	D	0.569	neutral	None	None	None	None	I
F/Q	0.8434	likely_pathogenic	0.8721	pathogenic	0.239	Stabilizing	0.997	D	0.567	neutral	None	None	None	None	I
F/R	0.772	likely_pathogenic	0.8139	pathogenic	0.54	Stabilizing	0.997	D	0.569	neutral	None	None	None	None	I
F/S	0.4375	ambiguous	0.465	ambiguous	-0.322	Destabilizing	0.92	D	0.571	neutral	N	0.469008066	None	None	I
F/T	0.5488	ambiguous	0.6132	pathogenic	-0.275	Destabilizing	0.969	D	0.572	neutral	None	None	None	None	I
F/V	0.1575	likely_benign	0.1911	benign	-0.288	Destabilizing	0.704	D	0.481	neutral	N	0.355394558	None	None	I
F/W	0.6196	likely_pathogenic	0.6535	pathogenic	-0.272	Destabilizing	0.999	D	0.459	neutral	None	None	None	None	I
F/Y	0.1778	likely_benign	0.1998	benign	-0.155	Destabilizing	0.986	D	0.425	neutral	N	0.455156121	None	None	I

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.