TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25736	77431;77432;77433	chr2:178568926;178568925;178568924	chr2:179433653;179433652;179433651
N2AB	24095	72508;72509;72510	chr2:178568926;178568925;178568924	chr2:179433653;179433652;179433651
N2A	23168	69727;69728;69729	chr2:178568926;178568925;178568924	chr2:179433653;179433652;179433651
N2B	16671	50236;50237;50238	chr2:178568926;178568925;178568924	chr2:179433653;179433652;179433651
Novex-1	16796	50611;50612;50613	chr2:178568926;178568925;178568924	chr2:179433653;179433652;179433651
Novex-2	16863	50812;50813;50814	chr2:178568926;178568925;178568924	chr2:179433653;179433652;179433651
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-75
• Domain position: 39
• Structural Position: 41
• Q(SASA): 0.1486
• 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
E/K	None	None	0.354	N	0.395	0.386	0.317378411342	gnomAD-4.0.0	1.59209E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8594E-06	0	0
E/Q	None	None	0.992	N	0.723	0.298	0.31411915649	gnomAD-4.0.0	1.59209E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43332E-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
E/A	0.783	likely_pathogenic	0.7773	pathogenic	-2.351	Highly Destabilizing	0.979	D	0.635	neutral	D	0.530583075	None	None	N
E/C	0.9798	likely_pathogenic	0.981	pathogenic	-1.373	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
E/D	0.6904	likely_pathogenic	0.6501	pathogenic	-1.784	Destabilizing	0.924	D	0.629	neutral	N	0.496603064	None	None	N
E/F	0.9849	likely_pathogenic	0.9843	pathogenic	-2.08	Highly Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
E/G	0.8957	likely_pathogenic	0.8851	pathogenic	-2.713	Highly Destabilizing	0.999	D	0.737	prob.delet.	D	0.532357501	None	None	N
E/H	0.9532	likely_pathogenic	0.9499	pathogenic	-1.863	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
E/I	0.9623	likely_pathogenic	0.9558	pathogenic	-1.292	Destabilizing	0.999	D	0.816	deleterious	None	None	None	None	N
E/K	0.9243	likely_pathogenic	0.9096	pathogenic	-2.16	Highly Destabilizing	0.354	N	0.395	neutral	N	0.505286343	None	None	N
E/L	0.9401	likely_pathogenic	0.9363	pathogenic	-1.292	Destabilizing	0.997	D	0.78	deleterious	None	None	None	None	N
E/M	0.9254	likely_pathogenic	0.9213	pathogenic	-0.452	Destabilizing	0.999	D	0.816	deleterious	None	None	None	None	N
E/N	0.9254	likely_pathogenic	0.9186	pathogenic	-2.228	Highly Destabilizing	0.994	D	0.796	deleterious	None	None	None	None	N
E/P	0.9995	likely_pathogenic	0.9995	pathogenic	-1.635	Destabilizing	0.991	D	0.79	deleterious	None	None	None	None	N
E/Q	0.4909	ambiguous	0.493	ambiguous	-1.972	Destabilizing	0.992	D	0.723	prob.delet.	N	0.472356289	None	None	N
E/R	0.9494	likely_pathogenic	0.9427	pathogenic	-1.86	Destabilizing	0.998	D	0.79	deleterious	None	None	None	None	N
E/S	0.8146	likely_pathogenic	0.7994	pathogenic	-2.983	Highly Destabilizing	0.992	D	0.673	neutral	None	None	None	None	N
E/T	0.9091	likely_pathogenic	0.8965	pathogenic	-2.632	Highly Destabilizing	0.998	D	0.767	deleterious	None	None	None	None	N
E/V	0.8961	likely_pathogenic	0.8824	pathogenic	-1.635	Destabilizing	0.995	D	0.759	deleterious	N	0.515214298	None	None	N
E/W	0.9945	likely_pathogenic	0.9936	pathogenic	-2.077	Highly Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
E/Y	0.9776	likely_pathogenic	0.9758	pathogenic	-1.91	Destabilizing	1.0	D	0.814	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.