TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17920	53983;53984;53985	chr2:178605537;178605536;178605535	chr2:179470264;179470263;179470262
N2AB	16279	49060;49061;49062	chr2:178605537;178605536;178605535	chr2:179470264;179470263;179470262
N2A	15352	46279;46280;46281	chr2:178605537;178605536;178605535	chr2:179470264;179470263;179470262
N2B	8855	26788;26789;26790	chr2:178605537;178605536;178605535	chr2:179470264;179470263;179470262
Novex-1	8980	27163;27164;27165	chr2:178605537;178605536;178605535	chr2:179470264;179470263;179470262
Novex-2	9047	27364;27365;27366	chr2:178605537;178605536;178605535	chr2:179470264;179470263;179470262
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: Fn3-18
• Domain position: 59
• Structural Position: 89
• Q(SASA): 0.389
• 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	0.852	N	0.444	0.402	0.483816155017	gnomAD-4.0.0	1.59419E-06	None	None	None	None	N	None	0	2.28791E-05	None	0	0	None	0	0	0	0	0
T/P	rs2054577412	None	0.996	N	0.595	0.439	0.473300991676	gnomAD-4.0.0	1.68045E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.8375E-05	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	0.0825	likely_benign	0.0949	benign	-1.027	Destabilizing	0.826	D	0.377	neutral	N	0.474562016	None	None	N
T/C	0.2755	likely_benign	0.3168	benign	-0.499	Destabilizing	0.999	D	0.526	neutral	None	None	None	None	N
T/D	0.5095	ambiguous	0.6256	pathogenic	-0.455	Destabilizing	0.939	D	0.541	neutral	None	None	None	None	N
T/E	0.3601	ambiguous	0.4529	ambiguous	-0.341	Destabilizing	0.884	D	0.433	neutral	None	None	None	None	N
T/F	0.3979	ambiguous	0.476	ambiguous	-0.947	Destabilizing	0.982	D	0.605	neutral	None	None	None	None	N
T/G	0.2046	likely_benign	0.2664	benign	-1.386	Destabilizing	0.969	D	0.511	neutral	None	None	None	None	N
T/H	0.2704	likely_benign	0.3552	ambiguous	-1.562	Destabilizing	0.998	D	0.549	neutral	None	None	None	None	N
T/I	0.2505	likely_benign	0.2935	benign	-0.12	Destabilizing	0.852	D	0.444	neutral	N	0.479489995	None	None	N
T/K	0.1424	likely_benign	0.1813	benign	-0.482	Destabilizing	0.852	D	0.437	neutral	N	0.502629489	None	None	N
T/L	0.08	likely_benign	0.0865	benign	-0.12	Destabilizing	0.02	N	0.234	neutral	None	None	None	None	N
T/M	0.0976	likely_benign	0.1015	benign	0.025	Stabilizing	0.373	N	0.265	neutral	None	None	None	None	N
T/N	0.1337	likely_benign	0.1683	benign	-0.834	Destabilizing	0.969	D	0.469	neutral	None	None	None	None	N
T/P	0.1009	likely_benign	0.125	benign	-0.389	Destabilizing	0.996	D	0.595	neutral	N	0.507536663	None	None	N
T/Q	0.1831	likely_benign	0.2381	benign	-0.74	Destabilizing	0.373	N	0.292	neutral	None	None	None	None	N
T/R	0.1199	likely_benign	0.1644	benign	-0.524	Destabilizing	0.92	D	0.555	neutral	N	0.495242157	None	None	N
T/S	0.1342	likely_benign	0.1707	benign	-1.143	Destabilizing	0.826	D	0.391	neutral	N	0.50684323	None	None	N
T/V	0.1512	likely_benign	0.1667	benign	-0.389	Destabilizing	0.759	D	0.387	neutral	None	None	None	None	N
T/W	0.7383	likely_pathogenic	0.8399	pathogenic	-0.982	Destabilizing	0.999	D	0.554	neutral	None	None	None	None	N
T/Y	0.4052	ambiguous	0.4922	ambiguous	-0.662	Destabilizing	0.997	D	0.582	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.