TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6543	19852;19853;19854	chr2:178728197;178728196;178728195	chr2:179592924;179592923;179592922
N2AB	6226	18901;18902;18903	chr2:178728197;178728196;178728195	chr2:179592924;179592923;179592922
N2A	5299	16120;16121;16122	chr2:178728197;178728196;178728195	chr2:179592924;179592923;179592922
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: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-49
• Domain position: 63
• Structural Position: 144
• Q(SASA): 0.0797
• 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
L/M	rs1578117153	-2.103	1.0	D	0.771	0.409	0.624477516964	gnomAD-4.0.0	1.59379E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02902E-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
L/A	0.6378	likely_pathogenic	0.7313	pathogenic	-2.707	Highly Destabilizing	0.999	D	0.681	prob.neutral	None	None	None	None	N
L/C	0.8054	likely_pathogenic	0.8413	pathogenic	-2.958	Highly Destabilizing	1.0	D	0.74	deleterious	None	None	None	None	N
L/D	0.9941	likely_pathogenic	0.9946	pathogenic	-3.481	Highly Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
L/E	0.9678	likely_pathogenic	0.971	pathogenic	-3.324	Highly Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
L/F	0.7552	likely_pathogenic	0.7603	pathogenic	-1.795	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
L/G	0.9378	likely_pathogenic	0.9501	pathogenic	-3.144	Highly Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
L/H	0.9597	likely_pathogenic	0.965	pathogenic	-2.283	Highly Destabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	N
L/I	0.1574	likely_benign	0.206	benign	-1.465	Destabilizing	0.999	D	0.546	neutral	None	None	None	None	N
L/K	0.9718	likely_pathogenic	0.9724	pathogenic	-2.261	Highly Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	N
L/M	0.2644	likely_benign	0.2821	benign	-1.835	Destabilizing	1.0	D	0.771	deleterious	D	0.528221623	None	None	N
L/N	0.9589	likely_pathogenic	0.9666	pathogenic	-2.626	Highly Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
L/P	0.8428	likely_pathogenic	0.8839	pathogenic	-1.861	Destabilizing	1.0	D	0.767	deleterious	N	0.504534734	None	None	N
L/Q	0.9035	likely_pathogenic	0.9191	pathogenic	-2.656	Highly Destabilizing	1.0	D	0.769	deleterious	D	0.546668273	None	None	N
L/R	0.9285	likely_pathogenic	0.9358	pathogenic	-1.754	Destabilizing	1.0	D	0.773	deleterious	D	0.546668273	None	None	N
L/S	0.8859	likely_pathogenic	0.9133	pathogenic	-3.266	Highly Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	N
L/T	0.4851	ambiguous	0.556	ambiguous	-2.976	Highly Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
L/V	0.1291	likely_benign	0.1665	benign	-1.861	Destabilizing	0.999	D	0.511	neutral	N	0.461479087	None	None	N
L/W	0.9332	likely_pathogenic	0.9275	pathogenic	-1.992	Destabilizing	1.0	D	0.661	neutral	None	None	None	None	N
L/Y	0.972	likely_pathogenic	0.9732	pathogenic	-1.799	Destabilizing	1.0	D	0.793	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.