TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5583	16972;16973;16974	chr2:178732222;178732221;178732220	chr2:179596949;179596948;179596947
N2AB	5266	16021;16022;16023	chr2:178732222;178732221;178732220	chr2:179596949;179596948;179596947
N2A	4339	13240;13241;13242	chr2:178732222;178732221;178732220	chr2:179596949;179596948;179596947
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-39
• Domain position: 41
• Structural Position: 56
• Q(SASA): 0.4975
• 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	None	None	0.999	N	0.633	0.333	0.564798353577	gnomAD-4.0.0	1.59117E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85811E-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
E/A	0.1518	likely_benign	0.1585	benign	-0.527	Destabilizing	0.999	D	0.665	neutral	N	0.488619299	None	None	N
E/C	0.8707	likely_pathogenic	0.8652	pathogenic	-0.436	Destabilizing	1.0	D	0.702	prob.neutral	None	None	None	None	N
E/D	0.3175	likely_benign	0.3167	benign	-0.565	Destabilizing	0.999	D	0.49	neutral	N	0.497062315	None	None	N
E/F	0.798	likely_pathogenic	0.7997	pathogenic	0.041	Stabilizing	1.0	D	0.682	prob.neutral	None	None	None	None	N
E/G	0.261	likely_benign	0.277	benign	-0.807	Destabilizing	1.0	D	0.646	neutral	D	0.527754324	None	None	N
E/H	0.5813	likely_pathogenic	0.5749	pathogenic	0.3	Stabilizing	1.0	D	0.637	neutral	None	None	None	None	N
E/I	0.2979	likely_benign	0.2899	benign	0.212	Stabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
E/K	0.1491	likely_benign	0.1466	benign	-0.039	Destabilizing	0.999	D	0.633	neutral	N	0.517396658	None	None	N
E/L	0.3472	ambiguous	0.3582	ambiguous	0.212	Stabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
E/M	0.3876	ambiguous	0.3925	ambiguous	0.193	Stabilizing	1.0	D	0.644	neutral	None	None	None	None	N
E/N	0.4211	ambiguous	0.4305	ambiguous	-0.618	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
E/P	0.3442	ambiguous	0.3566	ambiguous	-0.014	Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	N
E/Q	0.1414	likely_benign	0.1409	benign	-0.511	Destabilizing	1.0	D	0.601	neutral	N	0.487707473	None	None	N
E/R	0.283	likely_benign	0.2697	benign	0.387	Stabilizing	1.0	D	0.676	prob.neutral	None	None	None	None	N
E/S	0.3474	ambiguous	0.354	ambiguous	-0.805	Destabilizing	0.999	D	0.641	neutral	None	None	None	None	N
E/T	0.2949	likely_benign	0.3024	benign	-0.565	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	N
E/V	0.1762	likely_benign	0.1745	benign	-0.014	Destabilizing	1.0	D	0.693	prob.neutral	N	0.486999911	None	None	N
E/W	0.9181	likely_pathogenic	0.9184	pathogenic	0.314	Stabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
E/Y	0.7119	likely_pathogenic	0.7068	pathogenic	0.307	Stabilizing	1.0	D	0.661	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.