TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18230	54913;54914;54915	chr2:178603999;178603998;178603997	chr2:179468726;179468725;179468724
N2AB	16589	49990;49991;49992	chr2:178603999;178603998;178603997	chr2:179468726;179468725;179468724
N2A	15662	47209;47210;47211	chr2:178603999;178603998;178603997	chr2:179468726;179468725;179468724
N2B	9165	27718;27719;27720	chr2:178603999;178603998;178603997	chr2:179468726;179468725;179468724
Novex-1	9290	28093;28094;28095	chr2:178603999;178603998;178603997	chr2:179468726;179468725;179468724
Novex-2	9357	28294;28295;28296	chr2:178603999;178603998;178603997	chr2:179468726;179468725;179468724
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: Fn3-20
• Domain position: 65
• Structural Position: 90
• Q(SASA): 0.1543
• 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/V	None	None	0.999	N	0.849	0.473	0.500176316166	gnomAD-4.0.0	3.60097E-06	None	None	None	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
E/A	0.3804	ambiguous	0.2499	benign	-0.969	Destabilizing	0.996	D	0.575	neutral	N	0.501685339	None	None	N
E/C	0.9177	likely_pathogenic	0.9062	pathogenic	-0.429	Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
E/D	0.36	ambiguous	0.2249	benign	-1.144	Destabilizing	0.996	D	0.398	neutral	N	0.473209344	None	None	N
E/F	0.9394	likely_pathogenic	0.8859	pathogenic	-0.232	Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
E/G	0.5524	ambiguous	0.4046	ambiguous	-1.398	Destabilizing	0.999	D	0.755	deleterious	N	0.480464273	None	None	N
E/H	0.7713	likely_pathogenic	0.6604	pathogenic	-0.479	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
E/I	0.6567	likely_pathogenic	0.5165	ambiguous	0.232	Stabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
E/K	0.5676	likely_pathogenic	0.4409	ambiguous	-0.428	Destabilizing	0.992	D	0.455	neutral	N	0.49143106	None	None	N
E/L	0.7668	likely_pathogenic	0.6342	pathogenic	0.232	Stabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
E/M	0.7439	likely_pathogenic	0.6265	pathogenic	0.793	Stabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
E/N	0.6065	likely_pathogenic	0.4488	ambiguous	-1.076	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	N
E/P	0.9381	likely_pathogenic	0.877	pathogenic	-0.148	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
E/Q	0.2602	likely_benign	0.1978	benign	-0.873	Destabilizing	0.957	D	0.229	neutral	N	0.46995971	None	None	N
E/R	0.6424	likely_pathogenic	0.529	ambiguous	-0.246	Destabilizing	0.999	D	0.683	prob.neutral	None	None	None	None	N
E/S	0.4034	ambiguous	0.2843	benign	-1.514	Destabilizing	0.997	D	0.544	neutral	None	None	None	None	N
E/T	0.3776	ambiguous	0.2674	benign	-1.118	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
E/V	0.4315	ambiguous	0.3138	benign	-0.148	Destabilizing	0.999	D	0.849	deleterious	N	0.515636072	None	None	N
E/W	0.9841	likely_pathogenic	0.9658	pathogenic	0.087	Stabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
E/Y	0.8852	likely_pathogenic	0.7986	pathogenic	0.095	Stabilizing	1.0	D	0.903	deleterious	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.