TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15953	48082;48083;48084	chr2:178617138;178617137;178617136	chr2:179481865;179481864;179481863
N2AB	14312	43159;43160;43161	chr2:178617138;178617137;178617136	chr2:179481865;179481864;179481863
N2A	13385	40378;40379;40380	chr2:178617138;178617137;178617136	chr2:179481865;179481864;179481863
N2B	6888	20887;20888;20889	chr2:178617138;178617137;178617136	chr2:179481865;179481864;179481863
Novex-1	7013	21262;21263;21264	chr2:178617138;178617137;178617136	chr2:179481865;179481864;179481863
Novex-2	7080	21463;21464;21465	chr2:178617138;178617137;178617136	chr2:179481865;179481864;179481863
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: Fn3-3
• Domain position: 95
• Structural Position: 129
• Q(SASA): 0.205
• 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	None	None	0.376	N	0.494	0.095	0.260735089382	gnomAD-4.0.0	2.40098E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.62537E-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	0.0992	likely_benign	0.0906	benign	-0.754	Destabilizing	0.332	N	0.401	neutral	N	0.474112573	None	None	N
T/C	0.3768	ambiguous	0.3431	ambiguous	-0.429	Destabilizing	0.992	D	0.634	neutral	None	None	None	None	N
T/D	0.4225	ambiguous	0.406	ambiguous	-0.106	Destabilizing	0.972	D	0.581	neutral	None	None	None	None	N
T/E	0.2581	likely_benign	0.2427	benign	-0.139	Destabilizing	0.919	D	0.53	neutral	None	None	None	None	N
T/F	0.1905	likely_benign	0.1878	benign	-0.973	Destabilizing	0.737	D	0.665	prob.neutral	None	None	None	None	N
T/G	0.3896	ambiguous	0.3677	ambiguous	-0.968	Destabilizing	0.919	D	0.597	neutral	None	None	None	None	N
T/H	0.2518	likely_benign	0.2367	benign	-1.247	Destabilizing	0.992	D	0.731	deleterious	None	None	None	None	N
T/I	0.1048	likely_benign	0.1013	benign	-0.289	Destabilizing	0.376	N	0.494	neutral	N	0.472305662	None	None	N
T/K	0.1803	likely_benign	0.1661	benign	-0.647	Destabilizing	0.919	D	0.554	neutral	None	None	None	None	N
T/L	0.0631	likely_benign	0.0653	benign	-0.289	Destabilizing	0.001	N	0.298	neutral	None	None	None	None	N
T/M	0.0789	likely_benign	0.0738	benign	0.076	Stabilizing	0.848	D	0.605	neutral	None	None	None	None	N
T/N	0.1606	likely_benign	0.1545	benign	-0.497	Destabilizing	0.963	D	0.509	neutral	D	0.542528605	None	None	N
T/P	0.1244	likely_benign	0.1234	benign	-0.413	Destabilizing	0.963	D	0.603	neutral	D	0.583633004	None	None	N
T/Q	0.2105	likely_benign	0.1966	benign	-0.741	Destabilizing	0.972	D	0.623	neutral	None	None	None	None	N
T/R	0.1644	likely_benign	0.1575	benign	-0.342	Destabilizing	0.919	D	0.601	neutral	None	None	None	None	N
T/S	0.1604	likely_benign	0.1466	benign	-0.789	Destabilizing	0.709	D	0.468	neutral	D	0.540800874	None	None	N
T/V	0.0953	likely_benign	0.0939	benign	-0.413	Destabilizing	0.248	N	0.402	neutral	None	None	None	None	N
T/W	0.5064	ambiguous	0.4907	ambiguous	-0.879	Destabilizing	0.992	D	0.787	deleterious	None	None	None	None	N
T/Y	0.2283	likely_benign	0.2235	benign	-0.652	Destabilizing	0.919	D	0.717	prob.delet.	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.