TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32084	96475;96476;96477	chr2:178543894;178543893;178543892	chr2:179408621;179408620;179408619
N2AB	30443	91552;91553;91554	chr2:178543894;178543893;178543892	chr2:179408621;179408620;179408619
N2A	29516	88771;88772;88773	chr2:178543894;178543893;178543892	chr2:179408621;179408620;179408619
N2B	23019	69280;69281;69282	chr2:178543894;178543893;178543892	chr2:179408621;179408620;179408619
Novex-1	23144	69655;69656;69657	chr2:178543894;178543893;178543892	chr2:179408621;179408620;179408619
Novex-2	23211	69856;69857;69858	chr2:178543894;178543893;178543892	chr2:179408621;179408620;179408619
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-153
• Domain position: 68
• Structural Position: 155
• Q(SASA): 0.2237
• Site annotation: Phosphothreonine
• 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	0.201	N	0.455	0.224	0.141422826196	gnomAD-4.0.0	1.36848E-06	None	None	Phosphothreonine	None	N	None	0	0	None	0	0	None	0	0	1.79902E-06	0	0
T/I	None	None	0.004	N	0.288	0.18	0.253205268125	gnomAD-4.0.0	3.60097E-06	None	None	Phosphothreonine	None	N	None	0	0	None	0	0	None	0	0	3.9375E-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	0.1062	likely_benign	0.1052	benign	-1.31	Destabilizing	0.201	N	0.455	neutral	N	0.476295265	Phosphothreonine	None	N
T/C	0.315	likely_benign	0.323	benign	-0.879	Destabilizing	0.992	D	0.545	neutral	None	None	Phosphothreonine	None	N
T/D	0.5506	ambiguous	0.5209	ambiguous	-0.535	Destabilizing	0.92	D	0.534	neutral	None	None	Phosphothreonine	None	N
T/E	0.3633	ambiguous	0.3544	ambiguous	-0.417	Destabilizing	0.766	D	0.504	neutral	None	None	Phosphothreonine	None	N
T/F	0.2106	likely_benign	0.1932	benign	-1.242	Destabilizing	0.85	D	0.579	neutral	None	None	Phosphothreonine	None	N
T/G	0.3479	ambiguous	0.3428	ambiguous	-1.655	Destabilizing	0.766	D	0.531	neutral	None	None	Phosphothreonine	None	N
T/H	0.2069	likely_benign	0.2077	benign	-1.795	Destabilizing	0.992	D	0.607	neutral	None	None	Phosphothreonine	None	N
T/I	0.095	likely_benign	0.0905	benign	-0.435	Destabilizing	0.004	N	0.288	neutral	N	0.479800197	Phosphothreonine	None	N
T/K	0.2214	likely_benign	0.21	benign	-0.469	Destabilizing	0.549	D	0.487	neutral	N	0.493902857	Phosphothreonine	None	N
T/L	0.0951	likely_benign	0.0886	benign	-0.435	Destabilizing	0.048	N	0.405	neutral	None	None	Phosphothreonine	None	N
T/M	0.0821	likely_benign	0.0811	benign	-0.252	Destabilizing	0.048	N	0.389	neutral	None	None	Phosphothreonine	None	N
T/N	0.1503	likely_benign	0.1439	benign	-0.794	Destabilizing	0.92	D	0.506	neutral	None	None	Phosphothreonine	None	N
T/P	0.8814	likely_pathogenic	0.8279	pathogenic	-0.696	Destabilizing	0.963	D	0.529	neutral	N	0.519860836	Phosphothreonine	None	N
T/Q	0.2184	likely_benign	0.2204	benign	-0.785	Destabilizing	0.92	D	0.539	neutral	None	None	Phosphothreonine	None	N
T/R	0.1634	likely_benign	0.1515	benign	-0.507	Destabilizing	0.81	D	0.533	neutral	N	0.515470208	Phosphothreonine	None	N
T/S	0.1246	likely_benign	0.124	benign	-1.196	Destabilizing	0.549	D	0.497	neutral	N	0.51493149	Phosphothreonine	None	N
T/V	0.0846	likely_benign	0.0852	benign	-0.696	Destabilizing	0.002	N	0.169	neutral	None	None	Phosphothreonine	None	N
T/W	0.5716	likely_pathogenic	0.552	ambiguous	-1.153	Destabilizing	0.992	D	0.635	neutral	None	None	Phosphothreonine	None	N
T/Y	0.2635	likely_benign	0.2555	benign	-0.866	Destabilizing	0.92	D	0.594	neutral	None	None	Phosphothreonine	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.