TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28880	86863;86864;86865	chr2:178559494;178559493;178559492	chr2:179424221;179424220;179424219
N2AB	27239	81940;81941;81942	chr2:178559494;178559493;178559492	chr2:179424221;179424220;179424219
N2A	26312	79159;79160;79161	chr2:178559494;178559493;178559492	chr2:179424221;179424220;179424219
N2B	19815	59668;59669;59670	chr2:178559494;178559493;178559492	chr2:179424221;179424220;179424219
Novex-1	19940	60043;60044;60045	chr2:178559494;178559493;178559492	chr2:179424221;179424220;179424219
Novex-2	20007	60244;60245;60246	chr2:178559494;178559493;178559492	chr2:179424221;179424220;179424219
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: Fn3-98
• Domain position: 36
• Structural Position: 38
• Q(SASA): 0.1158
• 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	rs1244106142	-4.088	0.999	D	0.881	0.831	0.912682040746	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	1.14837E-04	0	None	0	0	None	0	None	0	0	0
Y/D	rs1244106142	-4.088	0.999	D	0.881	0.831	0.912682040746	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
Y/D	rs1244106142	-4.088	0.999	D	0.881	0.831	0.912682040746	gnomAD-4.0.0	6.57281E-06	None	None	None	None	N	None	2.41348E-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
Y/A	0.9961	likely_pathogenic	0.996	pathogenic	-3.453	Highly Destabilizing	0.988	D	0.798	deleterious	None	None	None	None	N
Y/C	0.9137	likely_pathogenic	0.9002	pathogenic	-2.051	Highly Destabilizing	1.0	D	0.834	deleterious	D	0.636082486	None	None	N
Y/D	0.9967	likely_pathogenic	0.997	pathogenic	-3.838	Highly Destabilizing	0.999	D	0.881	deleterious	D	0.636486095	None	None	N
Y/E	0.9991	likely_pathogenic	0.9992	pathogenic	-3.621	Highly Destabilizing	0.999	D	0.846	deleterious	None	None	None	None	N
Y/F	0.2348	likely_benign	0.2009	benign	-1.371	Destabilizing	0.884	D	0.624	neutral	D	0.551313823	None	None	N
Y/G	0.9898	likely_pathogenic	0.9906	pathogenic	-3.873	Highly Destabilizing	0.998	D	0.873	deleterious	None	None	None	None	N
Y/H	0.97	likely_pathogenic	0.9689	pathogenic	-2.552	Highly Destabilizing	0.998	D	0.69	prob.neutral	D	0.636082486	None	None	N
Y/I	0.9586	likely_pathogenic	0.9573	pathogenic	-2.036	Highly Destabilizing	0.023	N	0.582	neutral	None	None	None	None	N
Y/K	0.9982	likely_pathogenic	0.9984	pathogenic	-2.451	Highly Destabilizing	0.986	D	0.851	deleterious	None	None	None	None	N
Y/L	0.9317	likely_pathogenic	0.927	pathogenic	-2.036	Highly Destabilizing	0.189	N	0.71	prob.delet.	None	None	None	None	N
Y/M	0.9844	likely_pathogenic	0.9839	pathogenic	-1.801	Destabilizing	0.997	D	0.756	deleterious	None	None	None	None	N
Y/N	0.9753	likely_pathogenic	0.9786	pathogenic	-3.275	Highly Destabilizing	0.999	D	0.856	deleterious	D	0.636486095	None	None	N
Y/P	0.9992	likely_pathogenic	0.9991	pathogenic	-2.528	Highly Destabilizing	0.999	D	0.883	deleterious	None	None	None	None	N
Y/Q	0.9976	likely_pathogenic	0.9976	pathogenic	-3.008	Highly Destabilizing	0.998	D	0.757	deleterious	None	None	None	None	N
Y/R	0.9929	likely_pathogenic	0.993	pathogenic	-2.209	Highly Destabilizing	0.999	D	0.852	deleterious	None	None	None	None	N
Y/S	0.9835	likely_pathogenic	0.9834	pathogenic	-3.601	Highly Destabilizing	0.998	D	0.839	deleterious	D	0.636486095	None	None	N
Y/T	0.9935	likely_pathogenic	0.9933	pathogenic	-3.261	Highly Destabilizing	0.997	D	0.829	deleterious	None	None	None	None	N
Y/V	0.9461	likely_pathogenic	0.9451	pathogenic	-2.528	Highly Destabilizing	0.936	D	0.716	prob.delet.	None	None	None	None	N
Y/W	0.8505	likely_pathogenic	0.819	pathogenic	-0.633	Destabilizing	1.0	D	0.683	prob.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.