TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23644	71155;71156;71157	chr2:178575202;178575201;178575200	chr2:179439929;179439928;179439927
N2AB	22003	66232;66233;66234	chr2:178575202;178575201;178575200	chr2:179439929;179439928;179439927
N2A	21076	63451;63452;63453	chr2:178575202;178575201;178575200	chr2:179439929;179439928;179439927
N2B	14579	43960;43961;43962	chr2:178575202;178575201;178575200	chr2:179439929;179439928;179439927
Novex-1	14704	44335;44336;44337	chr2:178575202;178575201;178575200	chr2:179439929;179439928;179439927
Novex-2	14771	44536;44537;44538	chr2:178575202;178575201;178575200	chr2:179439929;179439928;179439927
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-130
• Domain position: 8
• Structural Position: 14
• Q(SASA): 0.8043
• 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
I/S	None	None	0.884	N	0.387	0.455	0.750485479121	gnomAD-4.0.0	1.59348E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88445E-05	0	0	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
I/A	0.4863	ambiguous	0.5354	ambiguous	-1.094	Destabilizing	0.373	N	0.354	neutral	None	None	None	None	N
I/C	0.8146	likely_pathogenic	0.8257	pathogenic	-0.745	Destabilizing	0.996	D	0.405	neutral	None	None	None	None	N
I/D	0.9275	likely_pathogenic	0.9419	pathogenic	-0.84	Destabilizing	0.984	D	0.438	neutral	None	None	None	None	N
I/E	0.8384	likely_pathogenic	0.8741	pathogenic	-0.876	Destabilizing	0.953	D	0.429	neutral	None	None	None	None	N
I/F	0.2324	likely_benign	0.2554	benign	-0.8	Destabilizing	0.884	D	0.363	neutral	N	0.489237955	None	None	N
I/G	0.8669	likely_pathogenic	0.8922	pathogenic	-1.341	Destabilizing	0.953	D	0.409	neutral	None	None	None	None	N
I/H	0.7118	likely_pathogenic	0.731	pathogenic	-0.506	Destabilizing	0.996	D	0.435	neutral	None	None	None	None	N
I/K	0.6765	likely_pathogenic	0.7251	pathogenic	-0.837	Destabilizing	0.953	D	0.422	neutral	None	None	None	None	N
I/L	0.1571	likely_benign	0.1757	benign	-0.52	Destabilizing	0.003	N	0.149	neutral	N	0.513817635	None	None	N
I/M	0.1328	likely_benign	0.1487	benign	-0.554	Destabilizing	0.884	D	0.421	neutral	N	0.520802323	None	None	N
I/N	0.563	ambiguous	0.6098	pathogenic	-0.648	Destabilizing	0.979	D	0.438	neutral	N	0.488223997	None	None	N
I/P	0.8831	likely_pathogenic	0.9009	pathogenic	-0.68	Destabilizing	0.984	D	0.436	neutral	None	None	None	None	N
I/Q	0.7065	likely_pathogenic	0.7396	pathogenic	-0.844	Destabilizing	0.984	D	0.443	neutral	None	None	None	None	N
I/R	0.5687	likely_pathogenic	0.6194	pathogenic	-0.218	Destabilizing	0.953	D	0.438	neutral	None	None	None	None	N
I/S	0.5127	ambiguous	0.5585	ambiguous	-1.108	Destabilizing	0.884	D	0.387	neutral	N	0.501907131	None	None	N
I/T	0.2257	likely_benign	0.2613	benign	-1.033	Destabilizing	0.684	D	0.344	neutral	N	0.440877315	None	None	N
I/V	0.0937	likely_benign	0.0998	benign	-0.68	Destabilizing	0.003	N	0.178	neutral	N	0.455902695	None	None	N
I/W	0.838	likely_pathogenic	0.8434	pathogenic	-0.85	Destabilizing	0.996	D	0.567	neutral	None	None	None	None	N
I/Y	0.632	likely_pathogenic	0.6572	pathogenic	-0.628	Destabilizing	0.953	D	0.401	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.