TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6119	18580;18581;18582	chr2:178729898;178729897;178729896	chr2:179594625;179594624;179594623
N2AB	5802	17629;17630;17631	chr2:178729898;178729897;178729896	chr2:179594625;179594624;179594623
N2A	4875	14848;14849;14850	chr2:178729898;178729897;178729896	chr2:179594625;179594624;179594623
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: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-45
• Domain position: 15
• Structural Position: 23
• Q(SASA): 0.3723
• 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
N/S	None	None	0.042	N	0.278	0.136	0.214338557667	gnomAD-4.0.0	4.77681E-06	None	None	None	None	I	None	0	2.29001E-05	None	0	0	None	1.88437E-05	0	2.8593E-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
N/A	0.1344	likely_benign	0.14	benign	-0.528	Destabilizing	0.025	N	0.303	neutral	None	None	None	None	I
N/C	0.2804	likely_benign	0.282	benign	0.247	Stabilizing	0.958	D	0.385	neutral	None	None	None	None	I
N/D	0.0976	likely_benign	0.0961	benign	0.057	Stabilizing	0.042	N	0.257	neutral	N	0.429508315	None	None	I
N/E	0.1268	likely_benign	0.1252	benign	0.062	Stabilizing	None	N	0.131	neutral	None	None	None	None	I
N/F	0.4257	ambiguous	0.429	ambiguous	-0.658	Destabilizing	0.497	N	0.457	neutral	None	None	None	None	I
N/G	0.1987	likely_benign	0.2071	benign	-0.766	Destabilizing	0.104	N	0.245	neutral	None	None	None	None	I
N/H	0.0875	likely_benign	0.0908	benign	-0.681	Destabilizing	0.602	D	0.254	neutral	N	0.489826055	None	None	I
N/I	0.1638	likely_benign	0.1548	benign	0.027	Stabilizing	0.096	N	0.457	neutral	N	0.432585906	None	None	I
N/K	0.0906	likely_benign	0.0897	benign	-0.034	Destabilizing	None	N	0.083	neutral	N	0.409421044	None	None	I
N/L	0.166	likely_benign	0.1643	benign	0.027	Stabilizing	None	N	0.17	neutral	None	None	None	None	I
N/M	0.221	likely_benign	0.2238	benign	0.406	Stabilizing	0.497	N	0.407	neutral	None	None	None	None	I
N/P	0.2464	likely_benign	0.248	benign	-0.129	Destabilizing	None	N	0.1	neutral	None	None	None	None	I
N/Q	0.136	likely_benign	0.1453	benign	-0.527	Destabilizing	0.124	N	0.214	neutral	None	None	None	None	I
N/R	0.1194	likely_benign	0.1237	benign	None	Stabilizing	0.055	N	0.209	neutral	None	None	None	None	I
N/S	0.0809	likely_benign	0.0816	benign	-0.389	Destabilizing	0.042	N	0.278	neutral	N	0.440570671	None	None	I
N/T	0.1108	likely_benign	0.1098	benign	-0.217	Destabilizing	0.081	N	0.251	neutral	N	0.444341694	None	None	I
N/V	0.1643	likely_benign	0.1598	benign	-0.129	Destabilizing	0.055	N	0.359	neutral	None	None	None	None	I
N/W	0.5658	likely_pathogenic	0.5777	pathogenic	-0.533	Destabilizing	0.958	D	0.409	neutral	None	None	None	None	I
N/Y	0.1238	likely_benign	0.1283	benign	-0.31	Destabilizing	0.822	D	0.454	neutral	N	0.46783463	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.