TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26424	79495;79496;79497	chr2:178566862;178566861;178566860	chr2:179431589;179431588;179431587
N2AB	24783	74572;74573;74574	chr2:178566862;178566861;178566860	chr2:179431589;179431588;179431587
N2A	23856	71791;71792;71793	chr2:178566862;178566861;178566860	chr2:179431589;179431588;179431587
N2B	17359	52300;52301;52302	chr2:178566862;178566861;178566860	chr2:179431589;179431588;179431587
Novex-1	17484	52675;52676;52677	chr2:178566862;178566861;178566860	chr2:179431589;179431588;179431587
Novex-2	17551	52876;52877;52878	chr2:178566862;178566861;178566860	chr2:179431589;179431588;179431587
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-80
• Domain position: 39
• Structural Position: 41
• Q(SASA): 0.1734
• 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/A	None	None	0.999	D	0.697	0.603	0.441324992753	gnomAD-4.0.0	1.59206E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43287E-05	0
E/K	rs1706064410	None	0.999	N	0.67	0.492	0.342400092842	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/K	rs1706064410	None	0.999	N	0.67	0.492	0.342400092842	gnomAD-4.0.0	6.57471E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.4705E-05	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
E/A	0.9521	likely_pathogenic	0.9468	pathogenic	-1.7	Destabilizing	0.999	D	0.697	prob.neutral	D	0.545724815	None	None	N
E/C	0.9944	likely_pathogenic	0.9927	pathogenic	-0.875	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
E/D	0.8241	likely_pathogenic	0.8558	pathogenic	-1.749	Destabilizing	0.999	D	0.635	neutral	N	0.498413489	None	None	N
E/F	0.9967	likely_pathogenic	0.9955	pathogenic	-1.373	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
E/G	0.9512	likely_pathogenic	0.9433	pathogenic	-2.079	Highly Destabilizing	1.0	D	0.778	deleterious	D	0.540751292	None	None	N
E/H	0.987	likely_pathogenic	0.9867	pathogenic	-1.267	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
E/I	0.9937	likely_pathogenic	0.9918	pathogenic	-0.603	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
E/K	0.97	likely_pathogenic	0.9676	pathogenic	-1.757	Destabilizing	0.999	D	0.67	neutral	N	0.51631348	None	None	N
E/L	0.9892	likely_pathogenic	0.9857	pathogenic	-0.603	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
E/M	0.9868	likely_pathogenic	0.9835	pathogenic	0.162	Stabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
E/N	0.9823	likely_pathogenic	0.982	pathogenic	-1.933	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
E/P	0.9999	likely_pathogenic	0.9999	pathogenic	-0.956	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
E/Q	0.7588	likely_pathogenic	0.7672	pathogenic	-1.638	Destabilizing	1.0	D	0.732	prob.delet.	N	0.478610487	None	None	N
E/R	0.9757	likely_pathogenic	0.976	pathogenic	-1.56	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
E/S	0.947	likely_pathogenic	0.943	pathogenic	-2.568	Highly Destabilizing	0.999	D	0.731	prob.delet.	None	None	None	None	N
E/T	0.9828	likely_pathogenic	0.9808	pathogenic	-2.209	Highly Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
E/V	0.9809	likely_pathogenic	0.9768	pathogenic	-0.956	Destabilizing	1.0	D	0.776	deleterious	D	0.528381029	None	None	N
E/W	0.9977	likely_pathogenic	0.9972	pathogenic	-1.458	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
E/Y	0.9944	likely_pathogenic	0.9928	pathogenic	-1.213	Destabilizing	1.0	D	0.811	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.