TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29428	88507;88508;88509	chr2:178556872;178556871;178556870	chr2:179421599;179421598;179421597
N2AB	27787	83584;83585;83586	chr2:178556872;178556871;178556870	chr2:179421599;179421598;179421597
N2A	26860	80803;80804;80805	chr2:178556872;178556871;178556870	chr2:179421599;179421598;179421597
N2B	20363	61312;61313;61314	chr2:178556872;178556871;178556870	chr2:179421599;179421598;179421597
Novex-1	20488	61687;61688;61689	chr2:178556872;178556871;178556870	chr2:179421599;179421598;179421597
Novex-2	20555	61888;61889;61890	chr2:178556872;178556871;178556870	chr2:179421599;179421598;179421597
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Fn3-102
• Domain position: 94
• Structural Position: 126
• Q(SASA): 0.365
• 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
P/S	None	None	1.0	N	0.863	0.347	0.346768085243	gnomAD-4.0.0	3.1833E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71608E-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
P/A	0.1529	likely_benign	0.1009	benign	-0.503	Destabilizing	0.999	D	0.834	deleterious	N	0.457453694	None	None	N
P/C	0.667	likely_pathogenic	0.4754	ambiguous	-0.727	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
P/D	0.7293	likely_pathogenic	0.5369	ambiguous	-0.195	Destabilizing	1.0	D	0.872	deleterious	None	None	None	None	N
P/E	0.5432	ambiguous	0.3627	ambiguous	-0.284	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
P/F	0.7384	likely_pathogenic	0.5449	ambiguous	-0.557	Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
P/G	0.5239	ambiguous	0.3666	ambiguous	-0.663	Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
P/H	0.3939	ambiguous	0.2472	benign	-0.087	Destabilizing	1.0	D	0.861	deleterious	N	0.478908023	None	None	N
P/I	0.5568	ambiguous	0.3749	ambiguous	-0.223	Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	N
P/K	0.4987	ambiguous	0.3293	benign	-0.467	Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
P/L	0.2642	likely_benign	0.1633	benign	-0.223	Destabilizing	1.0	D	0.89	deleterious	N	0.460977898	None	None	N
P/M	0.5132	ambiguous	0.3624	ambiguous	-0.408	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
P/N	0.5207	ambiguous	0.3545	ambiguous	-0.284	Destabilizing	1.0	D	0.917	deleterious	None	None	None	None	N
P/Q	0.3114	likely_benign	0.1884	benign	-0.491	Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
P/R	0.3521	ambiguous	0.2134	benign	0.051	Stabilizing	1.0	D	0.918	deleterious	N	0.478654533	None	None	N
P/S	0.2483	likely_benign	0.1546	benign	-0.694	Destabilizing	1.0	D	0.863	deleterious	N	0.460043299	None	None	N
P/T	0.2081	likely_benign	0.1346	benign	-0.676	Destabilizing	1.0	D	0.857	deleterious	N	0.50917338	None	None	N
P/V	0.3891	ambiguous	0.2559	benign	-0.281	Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
P/W	0.8671	likely_pathogenic	0.7151	pathogenic	-0.635	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
P/Y	0.7055	likely_pathogenic	0.5201	ambiguous	-0.343	Destabilizing	1.0	D	0.911	deleterious	None	None	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.