TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15045	45358;45359;45360	chr2:178621691;178621690;178621689	chr2:179486418;179486417;179486416
N2AB	13404	40435;40436;40437	chr2:178621691;178621690;178621689	chr2:179486418;179486417;179486416
N2A	12477	37654;37655;37656	chr2:178621691;178621690;178621689	chr2:179486418;179486417;179486416
N2B	5980	18163;18164;18165	chr2:178621691;178621690;178621689	chr2:179486418;179486417;179486416
Novex-1	6105	18538;18539;18540	chr2:178621691;178621690;178621689	chr2:179486418;179486417;179486416
Novex-2	6172	18739;18740;18741	chr2:178621691;178621690;178621689	chr2:179486418;179486417;179486416
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-102
• Domain position: 15
• Structural Position: 24
• Q(SASA): 0.406
• 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/A	None	None	0.027	D	0.403	0.135	0.208816687407	gnomAD-4.0.0	1.5949E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86346E-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	0.1026	likely_benign	0.1154	benign	-0.391	Destabilizing	0.027	N	0.403	neutral	D	0.546602554	None	None	N
T/C	0.6556	likely_pathogenic	0.6947	pathogenic	-0.021	Destabilizing	0.935	D	0.565	neutral	None	None	None	None	N
T/D	0.3451	ambiguous	0.405	ambiguous	-0.301	Destabilizing	0.081	N	0.477	neutral	None	None	None	None	N
T/E	0.3086	likely_benign	0.3642	ambiguous	-0.387	Destabilizing	0.149	N	0.457	neutral	None	None	None	None	N
T/F	0.3776	ambiguous	0.4546	ambiguous	-0.939	Destabilizing	0.791	D	0.59	neutral	None	None	None	None	N
T/G	0.2339	likely_benign	0.2473	benign	-0.516	Destabilizing	None	N	0.322	neutral	None	None	None	None	N
T/H	0.3453	ambiguous	0.3952	ambiguous	-0.918	Destabilizing	0.555	D	0.594	neutral	None	None	None	None	N
T/I	0.3333	likely_benign	0.4165	ambiguous	-0.175	Destabilizing	0.484	N	0.539	neutral	D	0.548472214	None	None	N
T/K	0.2111	likely_benign	0.2558	benign	-0.34	Destabilizing	0.062	N	0.443	neutral	N	0.453229929	None	None	N
T/L	0.17	likely_benign	0.2069	benign	-0.175	Destabilizing	0.149	N	0.481	neutral	None	None	None	None	N
T/M	0.1033	likely_benign	0.1149	benign	0.295	Stabilizing	0.791	D	0.561	neutral	None	None	None	None	N
T/N	0.1041	likely_benign	0.1189	benign	-0.076	Destabilizing	0.001	N	0.319	neutral	None	None	None	None	N
T/P	0.2924	likely_benign	0.3838	ambiguous	-0.22	Destabilizing	0.484	N	0.543	neutral	N	0.504327812	None	None	N
T/Q	0.2608	likely_benign	0.3004	benign	-0.416	Destabilizing	0.38	N	0.542	neutral	None	None	None	None	N
T/R	0.1814	likely_benign	0.2248	benign	0.013	Stabilizing	None	N	0.389	neutral	N	0.461301154	None	None	N
T/S	0.122	likely_benign	0.1368	benign	-0.226	Destabilizing	0.001	N	0.259	neutral	N	0.465285498	None	None	N
T/V	0.2799	likely_benign	0.3394	benign	-0.22	Destabilizing	0.149	N	0.361	neutral	None	None	None	None	N
T/W	0.6638	likely_pathogenic	0.7371	pathogenic	-0.933	Destabilizing	0.935	D	0.605	neutral	None	None	None	None	N
T/Y	0.3721	ambiguous	0.4448	ambiguous	-0.652	Destabilizing	0.791	D	0.591	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.