TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5307	16144;16145;16146	chr2:178733374;178733373;178733372	chr2:179598101;179598100;179598099
N2AB	4990	15193;15194;15195	chr2:178733374;178733373;178733372	chr2:179598101;179598100;179598099
N2A	4063	12412;12413;12414	chr2:178733374;178733373;178733372	chr2:179598101;179598100;179598099
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: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-36
• Domain position: 47
• Structural Position: 121
• Q(SASA): 0.1523
• 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/D	rs1349650603	-3.215	0.901	D	0.699	0.594	0.738898308675	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
Y/D	rs1349650603	-3.215	0.901	D	0.699	0.594	0.738898308675	gnomAD-4.0.0	1.59123E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8582E-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
Y/A	0.8366	likely_pathogenic	0.7986	pathogenic	-2.562	Highly Destabilizing	0.775	D	0.587	neutral	None	None	None	None	N
Y/C	0.2888	likely_benign	0.2331	benign	-1.605	Destabilizing	0.018	N	0.503	neutral	D	0.576164699	None	None	N
Y/D	0.8652	likely_pathogenic	0.8406	pathogenic	-2.147	Highly Destabilizing	0.901	D	0.699	prob.neutral	D	0.633562291	None	None	N
Y/E	0.9407	likely_pathogenic	0.9228	pathogenic	-1.955	Destabilizing	0.923	D	0.631	neutral	None	None	None	None	N
Y/F	0.1727	likely_benign	0.1603	benign	-0.832	Destabilizing	0.84	D	0.542	neutral	N	0.510265694	None	None	N
Y/G	0.7786	likely_pathogenic	0.7403	pathogenic	-2.975	Highly Destabilizing	0.923	D	0.648	neutral	None	None	None	None	N
Y/H	0.4888	ambiguous	0.3869	ambiguous	-1.479	Destabilizing	0.008	N	0.343	neutral	N	0.493472218	None	None	N
Y/I	0.7116	likely_pathogenic	0.6703	pathogenic	-1.231	Destabilizing	0.961	D	0.646	neutral	None	None	None	None	N
Y/K	0.9341	likely_pathogenic	0.9083	pathogenic	-1.917	Destabilizing	0.923	D	0.629	neutral	None	None	None	None	N
Y/L	0.7039	likely_pathogenic	0.6661	pathogenic	-1.231	Destabilizing	0.775	D	0.557	neutral	None	None	None	None	N
Y/M	0.7988	likely_pathogenic	0.7756	pathogenic	-1.04	Destabilizing	0.996	D	0.637	neutral	None	None	None	None	N
Y/N	0.5292	ambiguous	0.4688	ambiguous	-2.62	Highly Destabilizing	0.82	D	0.643	neutral	D	0.694703242	None	None	N
Y/P	0.9881	likely_pathogenic	0.9856	pathogenic	-1.682	Destabilizing	0.987	D	0.727	prob.delet.	None	None	None	None	N
Y/Q	0.8659	likely_pathogenic	0.8155	pathogenic	-2.332	Highly Destabilizing	0.923	D	0.674	neutral	None	None	None	None	N
Y/R	0.8754	likely_pathogenic	0.8285	pathogenic	-1.75	Destabilizing	0.923	D	0.681	prob.neutral	None	None	None	None	N
Y/S	0.6342	likely_pathogenic	0.5732	pathogenic	-3.102	Highly Destabilizing	0.901	D	0.629	neutral	D	0.586092347	None	None	N
Y/T	0.8026	likely_pathogenic	0.7598	pathogenic	-2.788	Highly Destabilizing	0.961	D	0.633	neutral	None	None	None	None	N
Y/V	0.6042	likely_pathogenic	0.5684	pathogenic	-1.682	Destabilizing	0.775	D	0.58	neutral	None	None	None	None	N
Y/W	0.6539	likely_pathogenic	0.6326	pathogenic	-0.219	Destabilizing	0.996	D	0.57	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.