TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30318	91177;91178;91179	chr2:178551948;178551947;178551946	chr2:179416675;179416674;179416673
N2AB	28677	86254;86255;86256	chr2:178551948;178551947;178551946	chr2:179416675;179416674;179416673
N2A	27750	83473;83474;83475	chr2:178551948;178551947;178551946	chr2:179416675;179416674;179416673
N2B	21253	63982;63983;63984	chr2:178551948;178551947;178551946	chr2:179416675;179416674;179416673
Novex-1	21378	64357;64358;64359	chr2:178551948;178551947;178551946	chr2:179416675;179416674;179416673
Novex-2	21445	64558;64559;64560	chr2:178551948;178551947;178551946	chr2:179416675;179416674;179416673
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Fn3-108
• Domain position: 95
• Structural Position: 130
• Q(SASA): 0.2199
• Predicted PPI site: I

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
A/G	rs774212641	-1.326	0.999	D	0.669	0.412	0.624893835469	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
A/G	rs774212641	-1.326	0.999	D	0.669	0.412	0.624893835469	gnomAD-4.0.0	3.18606E-06	None	None	None	None	I	None	0	2.28666E-05	None	0	0	None	0	0	2.86318E-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
A/C	0.6856	likely_pathogenic	0.7017	pathogenic	-1.57	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	I
A/D	0.9945	likely_pathogenic	0.9961	pathogenic	-2.612	Highly Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	I
A/E	0.9822	likely_pathogenic	0.9867	pathogenic	-2.495	Highly Destabilizing	1.0	D	0.849	deleterious	D	0.542326634	None	None	I
A/F	0.9417	likely_pathogenic	0.9616	pathogenic	-1.01	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	I
A/G	0.5106	ambiguous	0.5933	pathogenic	-1.689	Destabilizing	0.999	D	0.669	prob.neutral	D	0.524729358	None	None	I
A/H	0.9936	likely_pathogenic	0.9952	pathogenic	-1.886	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
A/I	0.5115	ambiguous	0.5853	pathogenic	-0.335	Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	I
A/K	0.994	likely_pathogenic	0.9957	pathogenic	-1.489	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	I
A/L	0.5686	likely_pathogenic	0.5968	pathogenic	-0.335	Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	I
A/M	0.6986	likely_pathogenic	0.7755	pathogenic	-0.587	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	I
A/N	0.9633	likely_pathogenic	0.9715	pathogenic	-1.66	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	I
A/P	0.6552	likely_pathogenic	0.7257	pathogenic	-0.619	Destabilizing	1.0	D	0.848	deleterious	N	0.515575098	None	None	I
A/Q	0.9663	likely_pathogenic	0.9751	pathogenic	-1.636	Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	I
A/R	0.983	likely_pathogenic	0.9859	pathogenic	-1.337	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	I
A/S	0.3359	likely_benign	0.3787	ambiguous	-2.019	Highly Destabilizing	0.999	D	0.707	prob.delet.	D	0.529538297	None	None	I
A/T	0.3751	ambiguous	0.4486	ambiguous	-1.801	Destabilizing	1.0	D	0.846	deleterious	N	0.48811232	None	None	I
A/V	0.2631	likely_benign	0.3344	benign	-0.619	Destabilizing	0.999	D	0.826	deleterious	D	0.53423298	None	None	I
A/W	0.996	likely_pathogenic	0.9971	pathogenic	-1.607	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	I
A/Y	0.9868	likely_pathogenic	0.991	pathogenic	-1.145	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	I

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.