TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32725	98398;98399;98400	chr2:178539892;178539891;178539890	chr2:179404619;179404618;179404617
N2AB	31084	93475;93476;93477	chr2:178539892;178539891;178539890	chr2:179404619;179404618;179404617
N2A	30157	90694;90695;90696	chr2:178539892;178539891;178539890	chr2:179404619;179404618;179404617
N2B	23660	71203;71204;71205	chr2:178539892;178539891;178539890	chr2:179404619;179404618;179404617
Novex-1	23785	71578;71579;71580	chr2:178539892;178539891;178539890	chr2:179404619;179404618;179404617
Novex-2	23852	71779;71780;71781	chr2:178539892;178539891;178539890	chr2:179404619;179404618;179404617
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-155
• Domain position: 18
• Structural Position: 31
• Q(SASA): 0.4508
• 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
T/N	None	None	0.004	N	0.299	0.145	0.269558022972	gnomAD-4.0.0	1.20033E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.66327E-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
T/A	0.0876	likely_benign	0.0783	benign	-0.867	Destabilizing	0.201	N	0.407	neutral	N	0.49725346	None	None	I
T/C	0.3347	likely_benign	0.3073	benign	-0.646	Destabilizing	0.992	D	0.515	neutral	None	None	None	None	I
T/D	0.4322	ambiguous	0.4093	ambiguous	-0.75	Destabilizing	0.447	N	0.459	neutral	None	None	None	None	I
T/E	0.3511	ambiguous	0.3241	benign	-0.614	Destabilizing	0.617	D	0.455	neutral	None	None	None	None	I
T/F	0.2711	likely_benign	0.2729	benign	-0.557	Destabilizing	0.972	D	0.584	neutral	None	None	None	None	I
T/G	0.26	likely_benign	0.2336	benign	-1.253	Destabilizing	0.25	N	0.507	neutral	None	None	None	None	I
T/H	0.2393	likely_benign	0.2287	benign	-1.372	Destabilizing	0.85	D	0.575	neutral	None	None	None	None	I
T/I	0.2036	likely_benign	0.1666	benign	0.114	Stabilizing	0.896	D	0.513	neutral	N	0.483556231	None	None	I
T/K	0.2518	likely_benign	0.2442	benign	-0.717	Destabilizing	0.447	N	0.447	neutral	None	None	None	None	I
T/L	0.1256	likely_benign	0.1165	benign	0.114	Stabilizing	0.617	D	0.455	neutral	None	None	None	None	I
T/M	0.1088	likely_benign	0.107	benign	0.094	Stabilizing	0.992	D	0.515	neutral	None	None	None	None	I
T/N	0.1239	likely_benign	0.119	benign	-1.12	Destabilizing	0.004	N	0.299	neutral	N	0.472048371	None	None	I
T/P	0.2055	likely_benign	0.1357	benign	-0.179	Destabilizing	0.896	D	0.517	neutral	N	0.43714915	None	None	I
T/Q	0.2319	likely_benign	0.2076	benign	-0.977	Destabilizing	0.85	D	0.517	neutral	None	None	None	None	I
T/R	0.1991	likely_benign	0.2018	benign	-0.752	Destabilizing	0.85	D	0.516	neutral	None	None	None	None	I
T/S	0.1068	likely_benign	0.1026	benign	-1.38	Destabilizing	0.007	N	0.226	neutral	N	0.429759031	None	None	I
T/V	0.1549	likely_benign	0.1355	benign	-0.179	Destabilizing	0.617	D	0.391	neutral	None	None	None	None	I
T/W	0.5772	likely_pathogenic	0.5836	pathogenic	-0.655	Destabilizing	0.992	D	0.618	neutral	None	None	None	None	I
T/Y	0.2681	likely_benign	0.2653	benign	-0.332	Destabilizing	0.972	D	0.582	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.