TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6521	19786;19787;19788	chr2:178728263;178728262;178728261	chr2:179592990;179592989;179592988
N2AB	6204	18835;18836;18837	chr2:178728263;178728262;178728261	chr2:179592990;179592989;179592988
N2A	5277	16054;16055;16056	chr2:178728263;178728262;178728261	chr2:179592990;179592989;179592988
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: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-49
• Domain position: 41
• Structural Position: 58
• Q(SASA): 0.1645
• 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
I/M	rs747626326	-0.335	0.012	D	0.416	0.224	0.312608672186	gnomAD-2.1.1	8.06E-06	None	None	None	None	N	None	0	5.81E-05	None	0	0	None	0	None	0	0	0
I/M	rs747626326	-0.335	0.012	D	0.416	0.224	0.312608672186	gnomAD-4.0.0	1.5924E-06	None	None	None	None	N	None	0	2.28875E-05	None	0	0	None	0	0	0	0	0
I/T	rs769180915	-2.113	0.062	D	0.492	0.49	0.660440515237	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
I/T	rs769180915	-2.113	0.062	D	0.492	0.49	0.660440515237	gnomAD-4.0.0	1.59237E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.4332E-05	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
I/A	0.855	likely_pathogenic	0.9139	pathogenic	-1.97	Destabilizing	0.035	N	0.455	neutral	None	None	None	None	N
I/C	0.9282	likely_pathogenic	0.9574	pathogenic	-1.076	Destabilizing	0.824	D	0.497	neutral	None	None	None	None	N
I/D	0.9791	likely_pathogenic	0.9886	pathogenic	-2.473	Highly Destabilizing	0.555	D	0.603	neutral	None	None	None	None	N
I/E	0.9618	likely_pathogenic	0.9768	pathogenic	-2.191	Highly Destabilizing	0.555	D	0.584	neutral	None	None	None	None	N
I/F	0.3172	likely_benign	0.3808	ambiguous	-1.222	Destabilizing	0.235	N	0.493	neutral	None	None	None	None	N
I/G	0.9603	likely_pathogenic	0.9781	pathogenic	-2.518	Highly Destabilizing	0.555	D	0.573	neutral	None	None	None	None	N
I/H	0.9398	likely_pathogenic	0.9651	pathogenic	-2.169	Highly Destabilizing	0.935	D	0.579	neutral	None	None	None	None	N
I/K	0.9042	likely_pathogenic	0.9407	pathogenic	-1.386	Destabilizing	0.317	N	0.573	neutral	D	0.55045739	None	None	N
I/L	0.106	likely_benign	0.1295	benign	-0.36	Destabilizing	None	N	0.128	neutral	N	0.487185608	None	None	N
I/M	0.1666	likely_benign	0.2146	benign	-0.338	Destabilizing	0.012	N	0.416	neutral	D	0.526730821	None	None	N
I/N	0.8388	likely_pathogenic	0.9043	pathogenic	-1.953	Destabilizing	0.555	D	0.611	neutral	None	None	None	None	N
I/P	0.9645	likely_pathogenic	0.9773	pathogenic	-0.881	Destabilizing	0.555	D	0.613	neutral	None	None	None	None	N
I/Q	0.9275	likely_pathogenic	0.9588	pathogenic	-1.67	Destabilizing	0.555	D	0.605	neutral	None	None	None	None	N
I/R	0.8708	likely_pathogenic	0.9209	pathogenic	-1.47	Destabilizing	0.484	N	0.615	neutral	D	0.543874024	None	None	N
I/S	0.9001	likely_pathogenic	0.948	pathogenic	-2.542	Highly Destabilizing	0.38	N	0.529	neutral	None	None	None	None	N
I/T	0.8619	likely_pathogenic	0.9224	pathogenic	-2.1	Highly Destabilizing	0.062	N	0.492	neutral	D	0.54083215	None	None	N
I/V	0.17	likely_benign	0.1905	benign	-0.881	Destabilizing	None	N	0.174	neutral	D	0.523015909	None	None	N
I/W	0.9244	likely_pathogenic	0.9529	pathogenic	-1.632	Destabilizing	0.935	D	0.613	neutral	None	None	None	None	N
I/Y	0.7764	likely_pathogenic	0.8357	pathogenic	-1.25	Destabilizing	0.555	D	0.551	neutral	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.