TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31274	94045;94046;94047	chr2:178547806;178547805;178547804	chr2:179412533;179412532;179412531
N2AB	29633	89122;89123;89124	chr2:178547806;178547805;178547804	chr2:179412533;179412532;179412531
N2A	28706	86341;86342;86343	chr2:178547806;178547805;178547804	chr2:179412533;179412532;179412531
N2B	22209	66850;66851;66852	chr2:178547806;178547805;178547804	chr2:179412533;179412532;179412531
Novex-1	22334	67225;67226;67227	chr2:178547806;178547805;178547804	chr2:179412533;179412532;179412531
Novex-2	22401	67426;67427;67428	chr2:178547806;178547805;178547804	chr2:179412533;179412532;179412531
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-151
• Domain position: 57
• Structural Position: 139
• Q(SASA): 0.2636
• 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
T/N	None	None	0.062	D	0.505	0.173	0.329282125956	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
T/A	0.074	likely_benign	0.0771	benign	-1.185	Destabilizing	0.027	N	0.395	neutral	N	0.487533343	None	None	N
T/C	0.2268	likely_benign	0.2293	benign	-0.87	Destabilizing	0.824	D	0.531	neutral	None	None	None	None	N
T/D	0.3754	ambiguous	0.3846	ambiguous	-0.813	Destabilizing	0.081	N	0.517	neutral	None	None	None	None	N
T/E	0.283	likely_benign	0.2779	benign	-0.69	Destabilizing	0.081	N	0.505	neutral	None	None	None	None	N
T/F	0.1644	likely_benign	0.1636	benign	-1.023	Destabilizing	0.38	N	0.573	neutral	None	None	None	None	N
T/G	0.2154	likely_benign	0.2262	benign	-1.538	Destabilizing	0.081	N	0.546	neutral	None	None	None	None	N
T/H	0.158	likely_benign	0.1627	benign	-1.687	Destabilizing	0.824	D	0.567	neutral	None	None	None	None	N
T/I	0.0939	likely_benign	0.1004	benign	-0.29	Destabilizing	0.027	N	0.543	neutral	N	0.447462144	None	None	N
T/K	0.1794	likely_benign	0.1777	benign	-0.553	Destabilizing	0.081	N	0.51	neutral	None	None	None	None	N
T/L	0.0718	likely_benign	0.0708	benign	-0.29	Destabilizing	None	N	0.305	neutral	None	None	None	None	N
T/M	0.07	likely_benign	0.074	benign	-0.188	Destabilizing	0.38	N	0.553	neutral	None	None	None	None	N
T/N	0.112	likely_benign	0.1195	benign	-0.915	Destabilizing	0.062	N	0.505	neutral	D	0.523288055	None	None	N
T/P	0.7017	likely_pathogenic	0.7154	pathogenic	-0.557	Destabilizing	0.317	N	0.543	neutral	N	0.48905428	None	None	N
T/Q	0.1711	likely_benign	0.1814	benign	-0.898	Destabilizing	0.38	N	0.548	neutral	None	None	None	None	N
T/R	0.1402	likely_benign	0.1385	benign	-0.579	Destabilizing	0.38	N	0.541	neutral	None	None	None	None	N
T/S	0.0873	likely_benign	0.09	benign	-1.242	Destabilizing	None	N	0.219	neutral	N	0.445827349	None	None	N
T/V	0.0895	likely_benign	0.0921	benign	-0.557	Destabilizing	0.002	N	0.227	neutral	None	None	None	None	N
T/W	0.4095	ambiguous	0.4099	ambiguous	-0.997	Destabilizing	0.935	D	0.589	neutral	None	None	None	None	N
T/Y	0.1938	likely_benign	0.188	benign	-0.689	Destabilizing	0.555	D	0.565	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.