TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18863	56812;56813;56814	chr2:178599206;178599205;178599204	chr2:179463933;179463932;179463931
N2AB	17222	51889;51890;51891	chr2:178599206;178599205;178599204	chr2:179463933;179463932;179463931
N2A	16295	49108;49109;49110	chr2:178599206;178599205;178599204	chr2:179463933;179463932;179463931
N2B	9798	29617;29618;29619	chr2:178599206;178599205;178599204	chr2:179463933;179463932;179463931
Novex-1	9923	29992;29993;29994	chr2:178599206;178599205;178599204	chr2:179463933;179463932;179463931
Novex-2	9990	30193;30194;30195	chr2:178599206;178599205;178599204	chr2:179463933;179463932;179463931
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-24
• Domain position: 80
• Structural Position: 112
• Q(SASA): 0.099
• 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
N/D	rs2052631045	None	0.999	D	0.613	0.765	0.453401982733	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
N/S	None	None	0.999	N	0.597	0.608	0.327419511103	gnomAD-4.0.0	1.86331E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.98035E-05	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
N/A	0.999	likely_pathogenic	0.999	pathogenic	-0.914	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
N/C	0.9807	likely_pathogenic	0.9817	pathogenic	-0.831	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	N
N/D	0.991	likely_pathogenic	0.99	pathogenic	-2.425	Highly Destabilizing	0.999	D	0.613	neutral	D	0.537667555	None	None	N
N/E	0.9986	likely_pathogenic	0.9985	pathogenic	-2.221	Highly Destabilizing	0.999	D	0.727	prob.delet.	None	None	None	None	N
N/F	0.9998	likely_pathogenic	0.9997	pathogenic	-0.79	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
N/G	0.993	likely_pathogenic	0.993	pathogenic	-1.216	Destabilizing	0.999	D	0.577	neutral	None	None	None	None	N
N/H	0.9897	likely_pathogenic	0.9891	pathogenic	-0.91	Destabilizing	1.0	D	0.773	deleterious	D	0.550798287	None	None	N
N/I	0.9978	likely_pathogenic	0.9977	pathogenic	-0.136	Destabilizing	1.0	D	0.816	deleterious	D	0.551051776	None	None	N
N/K	0.9987	likely_pathogenic	0.9986	pathogenic	-0.366	Destabilizing	1.0	D	0.752	deleterious	D	0.531680074	None	None	N
N/L	0.9934	likely_pathogenic	0.993	pathogenic	-0.136	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
N/M	0.9969	likely_pathogenic	0.9964	pathogenic	-0.064	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
N/P	0.9994	likely_pathogenic	0.9993	pathogenic	-0.371	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
N/Q	0.9986	likely_pathogenic	0.9986	pathogenic	-1.156	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
N/R	0.9982	likely_pathogenic	0.9983	pathogenic	-0.443	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
N/S	0.9481	likely_pathogenic	0.9477	pathogenic	-1.249	Destabilizing	0.999	D	0.597	neutral	N	0.50455969	None	None	N
N/T	0.9816	likely_pathogenic	0.9816	pathogenic	-0.902	Destabilizing	0.999	D	0.719	prob.delet.	N	0.488528896	None	None	N
N/V	0.9971	likely_pathogenic	0.9971	pathogenic	-0.371	Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
N/W	0.9999	likely_pathogenic	0.9999	pathogenic	-0.895	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
N/Y	0.9968	likely_pathogenic	0.9963	pathogenic	-0.44	Destabilizing	1.0	D	0.826	deleterious	D	0.550798287	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.