TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6447	19564;19565;19566	chr2:178728587;178728586;178728585	chr2:179593314;179593313;179593312
N2AB	6130	18613;18614;18615	chr2:178728587;178728586;178728585	chr2:179593314;179593313;179593312
N2A	5203	15832;15833;15834	chr2:178728587;178728586;178728585	chr2:179593314;179593313;179593312
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: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-48
• Domain position: 63
• Structural Position: 144
• Q(SASA): 0.1076
• 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
V/A	rs1270776568	None	0.116	N	0.162	0.22	0.52127940124	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
V/A	rs1270776568	None	0.116	N	0.162	0.22	0.52127940124	gnomAD-4.0.0	1.31482E-05	None	None	None	None	N	None	4.82789E-05	0	None	0	0	None	0	0	0	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
V/A	0.2677	likely_benign	0.2615	benign	-2.352	Highly Destabilizing	0.116	N	0.162	neutral	N	0.438591945	None	None	N
V/C	0.893	likely_pathogenic	0.9104	pathogenic	-2.047	Highly Destabilizing	1.0	D	0.557	neutral	None	None	None	None	N
V/D	0.9741	likely_pathogenic	0.9755	pathogenic	-3.298	Highly Destabilizing	0.995	D	0.627	neutral	None	None	None	None	N
V/E	0.9523	likely_pathogenic	0.953	pathogenic	-3.086	Highly Destabilizing	0.979	D	0.559	neutral	D	0.550981276	None	None	N
V/F	0.7502	likely_pathogenic	0.7884	pathogenic	-1.315	Destabilizing	0.999	D	0.625	neutral	None	None	None	None	N
V/G	0.6167	likely_pathogenic	0.6257	pathogenic	-2.856	Highly Destabilizing	0.959	D	0.537	neutral	N	0.51888737	None	None	N
V/H	0.9882	likely_pathogenic	0.99	pathogenic	-2.522	Highly Destabilizing	1.0	D	0.593	neutral	None	None	None	None	N
V/I	0.1218	likely_benign	0.1321	benign	-0.927	Destabilizing	0.906	D	0.517	neutral	D	0.533195617	None	None	N
V/K	0.9713	likely_pathogenic	0.974	pathogenic	-1.912	Destabilizing	0.984	D	0.582	neutral	None	None	None	None	N
V/L	0.4858	ambiguous	0.5209	ambiguous	-0.927	Destabilizing	0.906	D	0.469	neutral	D	0.532659686	None	None	N
V/M	0.4355	ambiguous	0.466	ambiguous	-1.132	Destabilizing	0.999	D	0.547	neutral	None	None	None	None	N
V/N	0.9115	likely_pathogenic	0.919	pathogenic	-2.304	Highly Destabilizing	0.995	D	0.625	neutral	None	None	None	None	N
V/P	0.8836	likely_pathogenic	0.9009	pathogenic	-1.38	Destabilizing	0.995	D	0.587	neutral	None	None	None	None	N
V/Q	0.9531	likely_pathogenic	0.9554	pathogenic	-2.153	Highly Destabilizing	0.999	D	0.609	neutral	None	None	None	None	N
V/R	0.9508	likely_pathogenic	0.9543	pathogenic	-1.696	Destabilizing	0.995	D	0.634	neutral	None	None	None	None	N
V/S	0.6094	likely_pathogenic	0.6256	pathogenic	-2.844	Highly Destabilizing	0.939	D	0.479	neutral	None	None	None	None	N
V/T	0.3942	ambiguous	0.3982	ambiguous	-2.506	Highly Destabilizing	0.293	N	0.246	neutral	None	None	None	None	N
V/W	0.9945	likely_pathogenic	0.9962	pathogenic	-1.861	Destabilizing	1.0	D	0.605	neutral	None	None	None	None	N
V/Y	0.9805	likely_pathogenic	0.9844	pathogenic	-1.571	Destabilizing	0.999	D	0.604	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.