TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31446	94561;94562;94563	chr2:178547189;178547188;178547187	chr2:179411916;179411915;179411914
N2AB	29805	89638;89639;89640	chr2:178547189;178547188;178547187	chr2:179411916;179411915;179411914
N2A	28878	86857;86858;86859	chr2:178547189;178547188;178547187	chr2:179411916;179411915;179411914
N2B	22381	67366;67367;67368	chr2:178547189;178547188;178547187	chr2:179411916;179411915;179411914
Novex-1	22506	67741;67742;67743	chr2:178547189;178547188;178547187	chr2:179411916;179411915;179411914
Novex-2	22573	67942;67943;67944	chr2:178547189;178547188;178547187	chr2:179411916;179411915;179411914
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: Fn3-117
• Domain position: 39
• Structural Position: 41
• Q(SASA): 0.119
• 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	0.701	0.551	0.481915485015	gnomAD-4.0.0	1.5912E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85827E-06	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	0.9744	likely_pathogenic	0.9716	pathogenic	-0.913	Destabilizing	0.999	D	0.701	prob.neutral	D	0.539470618	None	None	N
E/C	0.9963	likely_pathogenic	0.9957	pathogenic	-0.294	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
E/D	0.9686	likely_pathogenic	0.9586	pathogenic	-1.738	Destabilizing	0.999	D	0.645	neutral	N	0.478169641	None	None	N
E/F	0.9988	likely_pathogenic	0.9987	pathogenic	-0.6	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
E/G	0.9769	likely_pathogenic	0.9767	pathogenic	-1.315	Destabilizing	1.0	D	0.769	deleterious	D	0.52314079	None	None	N
E/H	0.996	likely_pathogenic	0.9952	pathogenic	-0.561	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
E/I	0.9963	likely_pathogenic	0.9961	pathogenic	0.232	Stabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
E/K	0.9883	likely_pathogenic	0.9872	pathogenic	-1.079	Destabilizing	0.999	D	0.683	prob.neutral	N	0.515325976	None	None	N
E/L	0.9957	likely_pathogenic	0.9953	pathogenic	0.232	Stabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
E/M	0.9939	likely_pathogenic	0.993	pathogenic	0.863	Stabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
E/N	0.9972	likely_pathogenic	0.9963	pathogenic	-1.428	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
E/P	0.9999	likely_pathogenic	0.9999	pathogenic	-0.134	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
E/Q	0.8908	likely_pathogenic	0.8728	pathogenic	-1.096	Destabilizing	1.0	D	0.749	deleterious	N	0.481079249	None	None	N
E/R	0.9897	likely_pathogenic	0.9898	pathogenic	-1.026	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
E/S	0.9855	likely_pathogenic	0.9828	pathogenic	-1.947	Destabilizing	0.999	D	0.746	deleterious	None	None	None	None	N
E/T	0.9948	likely_pathogenic	0.9939	pathogenic	-1.565	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
E/V	0.9894	likely_pathogenic	0.9887	pathogenic	-0.134	Destabilizing	1.0	D	0.77	deleterious	D	0.522126832	None	None	N
E/W	0.9994	likely_pathogenic	0.9993	pathogenic	-0.786	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
E/Y	0.9981	likely_pathogenic	0.9978	pathogenic	-0.425	Destabilizing	1.0	D	0.806	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.