TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6695	20308;20309;20310	chr2:178727282;178727281;178727280	chr2:179592009;179592008;179592007
N2AB	6378	19357;19358;19359	chr2:178727282;178727281;178727280	chr2:179592009;179592008;179592007
N2A	5451	16576;16577;16578	chr2:178727282;178727281;178727280	chr2:179592009;179592008;179592007
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: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-51
• Domain position: 29
• Structural Position: 42
• Q(SASA): 0.6684
• 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
P/L	None	None	0.936	D	0.523	0.504	0.728988515233	gnomAD-4.0.0	1.59292E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86118E-06	0	0
P/S	rs1278595517	-0.206	0.137	D	0.224	0.437	0.369867359543	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	2.91E-05	None	0	0	None	0	None	0	0	0
P/S	rs1278595517	-0.206	0.137	D	0.224	0.437	0.369867359543	gnomAD-4.0.0	1.59304E-06	None	None	None	None	I	None	0	2.29022E-05	None	0	0	None	0	0	0	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	0.5294	ambiguous	0.5606	ambiguous	-0.551	Destabilizing	0.016	N	0.201	neutral	D	0.538578695	None	None	I
P/C	0.9626	likely_pathogenic	0.9683	pathogenic	-0.612	Destabilizing	0.992	D	0.456	neutral	None	None	None	None	I
P/D	0.916	likely_pathogenic	0.9316	pathogenic	-0.46	Destabilizing	0.276	N	0.463	neutral	None	None	None	None	I
P/E	0.7841	likely_pathogenic	0.823	pathogenic	-0.579	Destabilizing	0.377	N	0.473	neutral	None	None	None	None	I
P/F	0.9783	likely_pathogenic	0.9832	pathogenic	-0.797	Destabilizing	0.998	D	0.484	neutral	None	None	None	None	I
P/G	0.8172	likely_pathogenic	0.8481	pathogenic	-0.68	Destabilizing	0.661	D	0.449	neutral	None	None	None	None	I
P/H	0.8012	likely_pathogenic	0.8458	pathogenic	-0.279	Destabilizing	0.998	D	0.429	neutral	None	None	None	None	I
P/I	0.9362	likely_pathogenic	0.9347	pathogenic	-0.364	Destabilizing	0.985	D	0.485	neutral	None	None	None	None	I
P/K	0.8543	likely_pathogenic	0.8979	pathogenic	-0.54	Destabilizing	0.906	D	0.431	neutral	None	None	None	None	I
P/L	0.7007	likely_pathogenic	0.7373	pathogenic	-0.364	Destabilizing	0.936	D	0.523	neutral	D	0.594366083	None	None	I
P/M	0.9086	likely_pathogenic	0.9198	pathogenic	-0.389	Destabilizing	0.998	D	0.429	neutral	None	None	None	None	I
P/N	0.8908	likely_pathogenic	0.9175	pathogenic	-0.25	Destabilizing	0.894	D	0.471	neutral	None	None	None	None	I
P/Q	0.6865	likely_pathogenic	0.7374	pathogenic	-0.513	Destabilizing	0.95	D	0.423	neutral	D	0.538578695	None	None	I
P/R	0.7068	likely_pathogenic	0.7683	pathogenic	0.007	Stabilizing	0.096	N	0.275	neutral	D	0.62321522	None	None	I
P/S	0.6598	likely_pathogenic	0.7175	pathogenic	-0.576	Destabilizing	0.137	N	0.224	neutral	D	0.534780033	None	None	I
P/T	0.5875	likely_pathogenic	0.6133	pathogenic	-0.599	Destabilizing	0.024	N	0.223	neutral	D	0.555423142	None	None	I
P/V	0.8483	likely_pathogenic	0.8432	pathogenic	-0.392	Destabilizing	0.772	D	0.484	neutral	None	None	None	None	I
P/W	0.9805	likely_pathogenic	0.9843	pathogenic	-0.877	Destabilizing	0.999	D	0.567	neutral	None	None	None	None	I
P/Y	0.9683	likely_pathogenic	0.9765	pathogenic	-0.586	Destabilizing	0.998	D	0.485	neutral	None	None	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.