TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18806	56641;56642;56643	chr2:178599377;178599376;178599375	chr2:179464104;179464103;179464102
N2AB	17165	51718;51719;51720	chr2:178599377;178599376;178599375	chr2:179464104;179464103;179464102
N2A	16238	48937;48938;48939	chr2:178599377;178599376;178599375	chr2:179464104;179464103;179464102
N2B	9741	29446;29447;29448	chr2:178599377;178599376;178599375	chr2:179464104;179464103;179464102
Novex-1	9866	29821;29822;29823	chr2:178599377;178599376;178599375	chr2:179464104;179464103;179464102
Novex-2	9933	30022;30023;30024	chr2:178599377;178599376;178599375	chr2:179464104;179464103;179464102
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: W
• RefSeq wild type transcript codon: TGG
• RefSeq wild type template codon: ACC
• Domain: Fn3-24
• Domain position: 23
• Structural Position: 24
• Q(SASA): 0.077
• 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
W/C	rs1042225014	-1.201	0.997	D	0.838	0.799	0.629801484396	gnomAD-2.1.1	4.34E-06	None	None	None	None	N	None	0	0	None	0	5.9E-05	None	0	None	0	0	0
W/C	rs1042225014	-1.201	0.997	D	0.838	0.799	0.629801484396	gnomAD-4.0.0	1.63607E-06	None	None	None	None	N	None	0	0	None	0	2.80065E-05	None	0	0	0	0	0
W/L	None	None	0.822	D	0.847	0.822	0.840916574304	gnomAD-4.0.0	6.92739E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.04593E-07	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
W/A	0.9946	likely_pathogenic	0.9909	pathogenic	-3.142	Highly Destabilizing	0.754	D	0.867	deleterious	None	None	None	None	N
W/C	0.9949	likely_pathogenic	0.992	pathogenic	-2.19	Highly Destabilizing	0.997	D	0.838	deleterious	D	0.656195064	None	None	N
W/D	0.9996	likely_pathogenic	0.9993	pathogenic	-3.799	Highly Destabilizing	0.956	D	0.884	deleterious	None	None	None	None	N
W/E	0.9996	likely_pathogenic	0.9994	pathogenic	-3.686	Highly Destabilizing	0.956	D	0.882	deleterious	None	None	None	None	N
W/F	0.7316	likely_pathogenic	0.6608	pathogenic	-2.07	Highly Destabilizing	0.978	D	0.767	deleterious	None	None	None	None	N
W/G	0.978	likely_pathogenic	0.9678	pathogenic	-3.381	Highly Destabilizing	0.698	D	0.843	deleterious	D	0.656195064	None	None	N
W/H	0.9958	likely_pathogenic	0.994	pathogenic	-2.482	Highly Destabilizing	0.994	D	0.855	deleterious	None	None	None	None	N
W/I	0.985	likely_pathogenic	0.9764	pathogenic	-2.22	Highly Destabilizing	0.978	D	0.886	deleterious	None	None	None	None	N
W/K	0.9997	likely_pathogenic	0.9996	pathogenic	-3.041	Highly Destabilizing	0.915	D	0.878	deleterious	None	None	None	None	N
W/L	0.9704	likely_pathogenic	0.956	pathogenic	-2.22	Highly Destabilizing	0.822	D	0.847	deleterious	D	0.638964877	None	None	N
W/M	0.9952	likely_pathogenic	0.9923	pathogenic	-1.772	Destabilizing	0.998	D	0.788	deleterious	None	None	None	None	N
W/N	0.9995	likely_pathogenic	0.9991	pathogenic	-3.834	Highly Destabilizing	0.915	D	0.888	deleterious	None	None	None	None	N
W/P	0.9985	likely_pathogenic	0.9982	pathogenic	-2.557	Highly Destabilizing	0.978	D	0.882	deleterious	None	None	None	None	N
W/Q	0.9997	likely_pathogenic	0.9995	pathogenic	-3.622	Highly Destabilizing	0.956	D	0.864	deleterious	None	None	None	None	N
W/R	0.999	likely_pathogenic	0.9984	pathogenic	-2.817	Highly Destabilizing	0.942	D	0.882	deleterious	D	0.656195064	None	None	N
W/S	0.992	likely_pathogenic	0.9863	pathogenic	-3.906	Highly Destabilizing	0.126	N	0.749	deleterious	D	0.656195064	None	None	N
W/T	0.9963	likely_pathogenic	0.9941	pathogenic	-3.719	Highly Destabilizing	0.915	D	0.838	deleterious	None	None	None	None	N
W/V	0.9844	likely_pathogenic	0.9745	pathogenic	-2.557	Highly Destabilizing	0.956	D	0.878	deleterious	None	None	None	None	N
W/Y	0.9316	likely_pathogenic	0.9011	pathogenic	-1.99	Destabilizing	0.993	D	0.771	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.