TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25160	75703;75704;75705	chr2:178570654;178570653;178570652	chr2:179435381;179435380;179435379
N2AB	23519	70780;70781;70782	chr2:178570654;178570653;178570652	chr2:179435381;179435380;179435379
N2A	22592	67999;68000;68001	chr2:178570654;178570653;178570652	chr2:179435381;179435380;179435379
N2B	16095	48508;48509;48510	chr2:178570654;178570653;178570652	chr2:179435381;179435380;179435379
Novex-1	16220	48883;48884;48885	chr2:178570654;178570653;178570652	chr2:179435381;179435380;179435379
Novex-2	16287	49084;49085;49086	chr2:178570654;178570653;178570652	chr2:179435381;179435380;179435379
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-134
• Domain position: 50
• Structural Position: 123
• Q(SASA): 0.2959
• 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
I/K	None	None	0.97	N	0.646	0.683	0.894683481021	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
I/A	0.7779	likely_pathogenic	0.8583	pathogenic	-2.277	Highly Destabilizing	0.86	D	0.467	neutral	None	None	None	None	N
I/C	0.8007	likely_pathogenic	0.8597	pathogenic	-1.724	Destabilizing	0.998	D	0.56	neutral	None	None	None	None	N
I/D	0.9566	likely_pathogenic	0.976	pathogenic	-1.562	Destabilizing	0.993	D	0.674	neutral	None	None	None	None	N
I/E	0.841	likely_pathogenic	0.9	pathogenic	-1.435	Destabilizing	0.978	D	0.662	neutral	None	None	None	None	N
I/F	0.2378	likely_benign	0.2842	benign	-1.492	Destabilizing	0.043	N	0.297	neutral	None	None	None	None	N
I/G	0.8983	likely_pathogenic	0.9421	pathogenic	-2.741	Highly Destabilizing	0.978	D	0.641	neutral	None	None	None	None	N
I/H	0.8205	likely_pathogenic	0.8834	pathogenic	-1.952	Destabilizing	0.998	D	0.685	prob.neutral	None	None	None	None	N
I/K	0.6493	likely_pathogenic	0.7511	pathogenic	-1.498	Destabilizing	0.97	D	0.646	neutral	N	0.51915995	None	None	N
I/L	0.1719	likely_benign	0.2099	benign	-0.998	Destabilizing	0.006	N	0.126	neutral	N	0.494784591	None	None	N
I/M	0.0989	likely_benign	0.1108	benign	-0.957	Destabilizing	0.942	D	0.501	neutral	N	0.493912444	None	None	N
I/N	0.6469	likely_pathogenic	0.7529	pathogenic	-1.516	Destabilizing	0.993	D	0.682	prob.neutral	None	None	None	None	N
I/P	0.9727	likely_pathogenic	0.9831	pathogenic	-1.399	Destabilizing	0.993	D	0.683	prob.neutral	None	None	None	None	N
I/Q	0.714	likely_pathogenic	0.797	pathogenic	-1.528	Destabilizing	0.993	D	0.681	prob.neutral	None	None	None	None	N
I/R	0.5862	likely_pathogenic	0.6978	pathogenic	-1.094	Destabilizing	0.97	D	0.679	prob.neutral	D	0.535542685	None	None	N
I/S	0.7549	likely_pathogenic	0.8392	pathogenic	-2.349	Highly Destabilizing	0.978	D	0.562	neutral	None	None	None	None	N
I/T	0.6909	likely_pathogenic	0.793	pathogenic	-2.075	Highly Destabilizing	0.822	D	0.512	neutral	N	0.518145992	None	None	N
I/V	0.1229	likely_benign	0.1452	benign	-1.399	Destabilizing	0.294	N	0.378	neutral	N	0.513526847	None	None	N
I/W	0.8009	likely_pathogenic	0.8411	pathogenic	-1.624	Destabilizing	0.998	D	0.701	prob.neutral	None	None	None	None	N
I/Y	0.606	likely_pathogenic	0.6895	pathogenic	-1.385	Destabilizing	0.915	D	0.529	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.