TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21384	64375;64376;64377	chr2:178586751;178586750;178586749	chr2:179451478;179451477;179451476
N2AB	19743	59452;59453;59454	chr2:178586751;178586750;178586749	chr2:179451478;179451477;179451476
N2A	18816	56671;56672;56673	chr2:178586751;178586750;178586749	chr2:179451478;179451477;179451476
N2B	12319	37180;37181;37182	chr2:178586751;178586750;178586749	chr2:179451478;179451477;179451476
Novex-1	12444	37555;37556;37557	chr2:178586751;178586750;178586749	chr2:179451478;179451477;179451476
Novex-2	12511	37756;37757;37758	chr2:178586751;178586750;178586749	chr2:179451478;179451477;179451476
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: Fn3-43
• Domain position: 19
• Structural Position: 21
• Q(SASA): 0.1668
• 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/I	rs2049065358	None	0.022	N	0.553	0.124	0.247872288689	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
T/I	rs2049065358	None	0.022	N	0.553	0.124	0.247872288689	gnomAD-4.0.0	6.5767E-06	None	None	None	None	N	None	0	6.55222E-05	None	0	0	None	0	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
T/A	0.1033	likely_benign	0.0893	benign	-0.925	Destabilizing	None	N	0.245	neutral	N	0.477106457	None	None	N
T/C	0.4053	ambiguous	0.3699	ambiguous	-0.818	Destabilizing	0.824	D	0.547	neutral	None	None	None	None	N
T/D	0.6683	likely_pathogenic	0.618	pathogenic	-0.914	Destabilizing	0.081	N	0.551	neutral	None	None	None	None	N
T/E	0.5019	ambiguous	0.4299	ambiguous	-0.879	Destabilizing	0.149	N	0.544	neutral	None	None	None	None	N
T/F	0.2267	likely_benign	0.1961	benign	-0.972	Destabilizing	0.38	N	0.588	neutral	None	None	None	None	N
T/G	0.3658	ambiguous	0.3207	benign	-1.2	Destabilizing	0.081	N	0.577	neutral	None	None	None	None	N
T/H	0.2699	likely_benign	0.2378	benign	-1.463	Destabilizing	0.824	D	0.57	neutral	None	None	None	None	N
T/I	0.131	likely_benign	0.1217	benign	-0.272	Destabilizing	0.022	N	0.553	neutral	N	0.475549521	None	None	N
T/K	0.2565	likely_benign	0.2178	benign	-0.778	Destabilizing	0.081	N	0.543	neutral	None	None	None	None	N
T/L	0.1045	likely_benign	0.0962	benign	-0.272	Destabilizing	0.081	N	0.538	neutral	None	None	None	None	N
T/M	0.1081	likely_benign	0.1044	benign	-0.009	Destabilizing	0.38	N	0.555	neutral	None	None	None	None	N
T/N	0.203	likely_benign	0.1846	benign	-0.924	Destabilizing	0.004	N	0.419	neutral	N	0.470118245	None	None	N
T/P	0.7242	likely_pathogenic	0.6905	pathogenic	-0.458	Destabilizing	0.317	N	0.585	neutral	N	0.513265742	None	None	N
T/Q	0.2877	likely_benign	0.2533	benign	-1.122	Destabilizing	0.38	N	0.585	neutral	None	None	None	None	N
T/R	0.2353	likely_benign	0.1964	benign	-0.539	Destabilizing	0.38	N	0.581	neutral	None	None	None	None	N
T/S	0.1263	likely_benign	0.1117	benign	-1.162	Destabilizing	0.002	N	0.429	neutral	N	0.494892653	None	None	N
T/V	0.0888	likely_benign	0.0854	benign	-0.458	Destabilizing	0.001	N	0.437	neutral	None	None	None	None	N
T/W	0.656	likely_pathogenic	0.6309	pathogenic	-0.911	Destabilizing	0.935	D	0.624	neutral	None	None	None	None	N
T/Y	0.2942	likely_benign	0.2558	benign	-0.637	Destabilizing	0.555	D	0.576	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.