TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6316	19171;19172;19173	chr2:178729092;178729091;178729090	chr2:179593819;179593818;179593817
N2AB	5999	18220;18221;18222	chr2:178729092;178729091;178729090	chr2:179593819;179593818;179593817
N2A	5072	15439;15440;15441	chr2:178729092;178729091;178729090	chr2:179593819;179593818;179593817
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: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-47
• Domain position: 25
• Structural Position: 38
• Q(SASA): 0.4148
• 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
A/G	None	None	0.201	N	0.326	0.069	0.185906805712	gnomAD-4.0.0	1.5959E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86421E-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
A/C	0.4226	ambiguous	0.4891	ambiguous	-0.81	Destabilizing	0.977	D	0.395	neutral	None	None	None	None	I
A/D	0.2422	likely_benign	0.2715	benign	0.058	Stabilizing	0.447	N	0.395	neutral	None	None	None	None	I
A/E	0.1681	likely_benign	0.194	benign	-0.02	Destabilizing	0.007	N	0.131	neutral	N	0.361147095	None	None	I
A/F	0.1958	likely_benign	0.2191	benign	-0.547	Destabilizing	0.85	D	0.406	neutral	None	None	None	None	I
A/G	0.1506	likely_benign	0.1592	benign	-0.451	Destabilizing	0.201	N	0.326	neutral	N	0.476147469	None	None	I
A/H	0.3031	likely_benign	0.3458	ambiguous	-0.448	Destabilizing	0.972	D	0.367	neutral	None	None	None	None	I
A/I	0.1433	likely_benign	0.1633	benign	-0.03	Destabilizing	0.217	N	0.381	neutral	None	None	None	None	I
A/K	0.2175	likely_benign	0.2603	benign	-0.626	Destabilizing	0.447	N	0.376	neutral	None	None	None	None	I
A/L	0.1167	likely_benign	0.1291	benign	-0.03	Destabilizing	0.25	N	0.381	neutral	None	None	None	None	I
A/M	0.1533	likely_benign	0.1638	benign	-0.298	Destabilizing	0.85	D	0.343	neutral	None	None	None	None	I
A/N	0.2024	likely_benign	0.2238	benign	-0.398	Destabilizing	0.617	D	0.39	neutral	None	None	None	None	I
A/P	0.7315	likely_pathogenic	0.809	pathogenic	-0.077	Destabilizing	0.896	D	0.385	neutral	N	0.491012382	None	None	I
A/Q	0.2161	likely_benign	0.2433	benign	-0.512	Destabilizing	0.85	D	0.394	neutral	None	None	None	None	I
A/R	0.1917	likely_benign	0.2242	benign	-0.352	Destabilizing	0.012	N	0.185	neutral	None	None	None	None	I
A/S	0.0844	likely_benign	0.0857	benign	-0.764	Destabilizing	0.016	N	0.127	neutral	N	0.416347017	None	None	I
A/T	0.0701	likely_benign	0.0726	benign	-0.727	Destabilizing	0.002	N	0.062	neutral	N	0.395683743	None	None	I
A/V	0.089	likely_benign	0.0971	benign	-0.077	Destabilizing	0.004	N	0.163	neutral	N	0.465295757	None	None	I
A/W	0.5473	ambiguous	0.6011	pathogenic	-0.788	Destabilizing	0.992	D	0.467	neutral	None	None	None	None	I
A/Y	0.3018	likely_benign	0.3441	ambiguous	-0.386	Destabilizing	0.92	D	0.404	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.