TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33029	99310;99311;99312	chr2:178538744;178538743;178538742	chr2:179403471;179403470;179403469
N2AB	31388	94387;94388;94389	chr2:178538744;178538743;178538742	chr2:179403471;179403470;179403469
N2A	30461	91606;91607;91608	chr2:178538744;178538743;178538742	chr2:179403471;179403470;179403469
N2B	23964	72115;72116;72117	chr2:178538744;178538743;178538742	chr2:179403471;179403470;179403469
Novex-1	24089	72490;72491;72492	chr2:178538744;178538743;178538742	chr2:179403471;179403470;179403469
Novex-2	24156	72691;72692;72693	chr2:178538744;178538743;178538742	chr2:179403471;179403470;179403469
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-129
• Domain position: 32
• Structural Position: 34
• Q(SASA): 0.5328
• 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
E/K	rs1431873084	0.142	0.645	N	0.526	0.304	0.230578612272	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
E/K	rs1431873084	0.142	0.645	N	0.526	0.304	0.230578612272	gnomAD-4.0.0	1.59141E-06	None	None	None	None	N	None	0	2.28645E-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
E/A	0.1371	likely_benign	0.1512	benign	-0.393	Destabilizing	0.645	D	0.569	neutral	N	0.455702334	None	None	N
E/C	0.7731	likely_pathogenic	0.8027	pathogenic	-0.249	Destabilizing	0.995	D	0.699	prob.neutral	None	None	None	None	N
E/D	0.0663	likely_benign	0.0727	benign	-0.398	Destabilizing	0.002	N	0.162	neutral	N	0.483464938	None	None	N
E/F	0.7784	likely_pathogenic	0.8103	pathogenic	-0.099	Destabilizing	0.995	D	0.661	neutral	None	None	None	None	N
E/G	0.1554	likely_benign	0.1704	benign	-0.626	Destabilizing	0.645	D	0.535	neutral	N	0.487545393	None	None	N
E/H	0.4967	ambiguous	0.519	ambiguous	0.134	Stabilizing	0.985	D	0.591	neutral	None	None	None	None	N
E/I	0.393	ambiguous	0.4304	ambiguous	0.197	Stabilizing	0.945	D	0.684	prob.neutral	None	None	None	None	N
E/K	0.2147	likely_benign	0.209	benign	0.099	Stabilizing	0.645	D	0.526	neutral	N	0.444138546	None	None	N
E/L	0.4061	ambiguous	0.4532	ambiguous	0.197	Stabilizing	0.945	D	0.679	prob.neutral	None	None	None	None	N
E/M	0.4741	ambiguous	0.5232	ambiguous	0.187	Stabilizing	0.995	D	0.633	neutral	None	None	None	None	N
E/N	0.1604	likely_benign	0.1742	benign	-0.265	Destabilizing	0.809	D	0.555	neutral	None	None	None	None	N
E/P	0.2493	likely_benign	0.2824	benign	0.021	Stabilizing	0.945	D	0.619	neutral	None	None	None	None	N
E/Q	0.1773	likely_benign	0.1861	benign	-0.198	Destabilizing	0.864	D	0.541	neutral	N	0.498703749	None	None	N
E/R	0.3348	likely_benign	0.3368	benign	0.41	Stabilizing	0.894	D	0.617	neutral	None	None	None	None	N
E/S	0.1679	likely_benign	0.1856	benign	-0.452	Destabilizing	0.547	D	0.527	neutral	None	None	None	None	N
E/T	0.2076	likely_benign	0.2328	benign	-0.262	Destabilizing	0.894	D	0.557	neutral	None	None	None	None	N
E/V	0.2228	likely_benign	0.2433	benign	0.021	Stabilizing	0.928	D	0.643	neutral	N	0.50776595	None	None	N
E/W	0.8971	likely_pathogenic	0.9147	pathogenic	0.084	Stabilizing	0.995	D	0.705	prob.neutral	None	None	None	None	N
E/Y	0.5849	likely_pathogenic	0.6188	pathogenic	0.143	Stabilizing	0.995	D	0.639	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.