TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27650	83173;83174;83175	chr2:178563184;178563183;178563182	chr2:179427911;179427910;179427909
N2AB	26009	78250;78251;78252	chr2:178563184;178563183;178563182	chr2:179427911;179427910;179427909
N2A	25082	75469;75470;75471	chr2:178563184;178563183;178563182	chr2:179427911;179427910;179427909
N2B	18585	55978;55979;55980	chr2:178563184;178563183;178563182	chr2:179427911;179427910;179427909
Novex-1	18710	56353;56354;56355	chr2:178563184;178563183;178563182	chr2:179427911;179427910;179427909
Novex-2	18777	56554;56555;56556	chr2:178563184;178563183;178563182	chr2:179427911;179427910;179427909
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: Fn3-89
• Domain position: 81
• Structural Position: 112
• Q(SASA): 0.1026
• 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/K	rs750669364	-0.356	0.919	N	0.605	0.321	0.230578612272	gnomAD-2.1.1	1.61E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	3.56E-05	0
N/K	rs750669364	-0.356	0.919	N	0.605	0.321	0.230578612272	gnomAD-4.0.0	1.43224E-05	None	None	None	None	N	None	0	0	None	0	0	None	1.88232E-05	0	1.71526E-05	0	6.04924E-05

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	0.9918	likely_pathogenic	0.9894	pathogenic	-0.363	Destabilizing	0.968	D	0.767	deleterious	None	None	None	None	N
N/C	0.9507	likely_pathogenic	0.9343	pathogenic	-0.345	Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
N/D	0.9848	likely_pathogenic	0.9828	pathogenic	-2.181	Highly Destabilizing	0.979	D	0.633	neutral	D	0.531271546	None	None	N
N/E	0.9985	likely_pathogenic	0.9984	pathogenic	-2.01	Highly Destabilizing	0.968	D	0.658	neutral	None	None	None	None	N
N/F	0.9988	likely_pathogenic	0.9987	pathogenic	-0.261	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
N/G	0.9754	likely_pathogenic	0.9715	pathogenic	-0.685	Destabilizing	0.968	D	0.589	neutral	None	None	None	None	N
N/H	0.9649	likely_pathogenic	0.9543	pathogenic	-0.535	Destabilizing	0.994	D	0.696	prob.neutral	D	0.561746064	None	None	N
N/I	0.9896	likely_pathogenic	0.9876	pathogenic	0.453	Stabilizing	0.994	D	0.828	deleterious	D	0.550896738	None	None	N
N/K	0.9983	likely_pathogenic	0.998	pathogenic	-0.119	Destabilizing	0.919	D	0.605	neutral	N	0.517535384	None	None	N
N/L	0.959	likely_pathogenic	0.9508	pathogenic	0.453	Stabilizing	0.991	D	0.815	deleterious	None	None	None	None	N
N/M	0.9934	likely_pathogenic	0.9916	pathogenic	0.614	Stabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
N/P	0.9953	likely_pathogenic	0.9942	pathogenic	0.21	Stabilizing	0.998	D	0.819	deleterious	None	None	None	None	N
N/Q	0.9975	likely_pathogenic	0.997	pathogenic	-0.986	Destabilizing	0.991	D	0.763	deleterious	None	None	None	None	N
N/R	0.9947	likely_pathogenic	0.9943	pathogenic	-0.211	Destabilizing	0.18	N	0.359	neutral	None	None	None	None	N
N/S	0.6157	likely_pathogenic	0.5412	ambiguous	-0.909	Destabilizing	0.958	D	0.59	neutral	N	0.514746999	None	None	N
N/T	0.9269	likely_pathogenic	0.8976	pathogenic	-0.588	Destabilizing	0.958	D	0.675	prob.neutral	N	0.507564068	None	None	N
N/V	0.9878	likely_pathogenic	0.9851	pathogenic	0.21	Stabilizing	0.995	D	0.831	deleterious	None	None	None	None	N
N/W	0.9997	likely_pathogenic	0.9996	pathogenic	-0.354	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
N/Y	0.991	likely_pathogenic	0.9894	pathogenic	0.129	Stabilizing	0.998	D	0.839	deleterious	D	0.561999554	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.