TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31087	93484;93485;93486	chr2:178548367;178548366;178548365	chr2:179413094;179413093;179413092
N2AB	29446	88561;88562;88563	chr2:178548367;178548366;178548365	chr2:179413094;179413093;179413092
N2A	28519	85780;85781;85782	chr2:178548367;178548366;178548365	chr2:179413094;179413093;179413092
N2B	22022	66289;66290;66291	chr2:178548367;178548366;178548365	chr2:179413094;179413093;179413092
Novex-1	22147	66664;66665;66666	chr2:178548367;178548366;178548365	chr2:179413094;179413093;179413092
Novex-2	22214	66865;66866;66867	chr2:178548367;178548366;178548365	chr2:179413094;179413093;179413092
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-114
• Domain position: 72
• Structural Position: 105
• Q(SASA): 0.2322
• 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
Y/S	rs901131458	None	0.891	N	0.584	0.28	0.723393103801	gnomAD-4.0.0	2.05256E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79888E-06	0	1.65645E-05

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
Y/A	0.5997	likely_pathogenic	0.5861	pathogenic	-3.285	Highly Destabilizing	0.688	D	0.565	neutral	None	None	None	None	N
Y/C	0.1187	likely_benign	0.1386	benign	-1.512	Destabilizing	0.997	D	0.64	neutral	N	0.513670415	None	None	N
Y/D	0.7508	likely_pathogenic	0.7062	pathogenic	-3.393	Highly Destabilizing	0.966	D	0.644	neutral	N	0.468215233	None	None	N
Y/E	0.9042	likely_pathogenic	0.8816	pathogenic	-3.238	Highly Destabilizing	0.915	D	0.628	neutral	None	None	None	None	N
Y/F	0.0791	likely_benign	0.0727	benign	-1.34	Destabilizing	0.005	N	0.23	neutral	N	0.434940272	None	None	N
Y/G	0.6172	likely_pathogenic	0.5996	pathogenic	-3.608	Highly Destabilizing	0.915	D	0.577	neutral	None	None	None	None	N
Y/H	0.2575	likely_benign	0.2455	benign	-2.118	Highly Destabilizing	0.989	D	0.581	neutral	N	0.508936599	None	None	N
Y/I	0.4997	ambiguous	0.4548	ambiguous	-2.198	Highly Destabilizing	0.728	D	0.559	neutral	None	None	None	None	N
Y/K	0.8482	likely_pathogenic	0.8142	pathogenic	-2.121	Highly Destabilizing	0.915	D	0.625	neutral	None	None	None	None	N
Y/L	0.4086	ambiguous	0.3658	ambiguous	-2.198	Highly Destabilizing	0.007	N	0.334	neutral	None	None	None	None	N
Y/M	0.6257	likely_pathogenic	0.6124	pathogenic	-1.732	Destabilizing	0.949	D	0.587	neutral	None	None	None	None	N
Y/N	0.3874	ambiguous	0.3962	ambiguous	-2.672	Highly Destabilizing	0.989	D	0.642	neutral	N	0.468313684	None	None	N
Y/P	0.9862	likely_pathogenic	0.98	pathogenic	-2.574	Highly Destabilizing	0.016	N	0.613	neutral	None	None	None	None	N
Y/Q	0.6898	likely_pathogenic	0.666	pathogenic	-2.569	Highly Destabilizing	0.991	D	0.589	neutral	None	None	None	None	N
Y/R	0.6705	likely_pathogenic	0.6176	pathogenic	-1.649	Destabilizing	0.991	D	0.644	neutral	None	None	None	None	N
Y/S	0.3137	likely_benign	0.3232	benign	-2.974	Highly Destabilizing	0.891	D	0.584	neutral	N	0.50612558	None	None	N
Y/T	0.5584	ambiguous	0.5389	ambiguous	-2.736	Highly Destabilizing	0.915	D	0.578	neutral	None	None	None	None	N
Y/V	0.3956	ambiguous	0.3647	ambiguous	-2.574	Highly Destabilizing	0.525	D	0.527	neutral	None	None	None	None	N
Y/W	0.5181	ambiguous	0.4767	ambiguous	-0.712	Destabilizing	0.991	D	0.598	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.