TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30439	91540;91541;91542	chr2:178551216;178551215;178551214	chr2:179415943;179415942;179415941
N2AB	28798	86617;86618;86619	chr2:178551216;178551215;178551214	chr2:179415943;179415942;179415941
N2A	27871	83836;83837;83838	chr2:178551216;178551215;178551214	chr2:179415943;179415942;179415941
N2B	21374	64345;64346;64347	chr2:178551216;178551215;178551214	chr2:179415943;179415942;179415941
Novex-1	21499	64720;64721;64722	chr2:178551216;178551215;178551214	chr2:179415943;179415942;179415941
Novex-2	21566	64921;64922;64923	chr2:178551216;178551215;178551214	chr2:179415943;179415942;179415941
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-110
• Domain position: 18
• Structural Position: 20
• Q(SASA): 0.0635
• 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
I/M	rs544097378	-1.306	0.901	N	0.677	0.245	0.392855499163	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
I/M	rs544097378	-1.306	0.901	N	0.677	0.245	0.392855499163	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
I/M	rs544097378	-1.306	0.901	N	0.677	0.245	0.392855499163	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	1.4E-03	None	None	0	0	None	None	None	0	None
I/M	rs544097378	-1.306	0.901	N	0.677	0.245	0.392855499163	gnomAD-4.0.0	6.56875E-06	None	None	None	None	N	None	0	6.54622E-05	None	0	0	None	0	0	0	0	0
I/S	rs561319486	-3.186	0.901	N	0.804	0.45	0.817238163268	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
I/S	rs561319486	-3.186	0.901	N	0.804	0.45	0.817238163268	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
I/S	rs561319486	-3.186	0.901	N	0.804	0.45	0.817238163268	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	0	1E-03	None	None	None	0	None
I/S	rs561319486	-3.186	0.901	N	0.804	0.45	0.817238163268	gnomAD-4.0.0	2.56304E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.78758E-06	0	0
I/T	rs561319486	None	0.722	D	0.776	0.37	0.610638308677	gnomAD-4.0.0	2.38819E-05	None	None	None	None	N	None	0	0	None	0	3.88522E-04	None	0	0	0	0	3.0248E-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
I/A	0.8016	likely_pathogenic	0.8516	pathogenic	-2.823	Highly Destabilizing	0.415	N	0.698	prob.neutral	None	None	None	None	N
I/C	0.8982	likely_pathogenic	0.9137	pathogenic	-2.422	Highly Destabilizing	0.989	D	0.807	deleterious	None	None	None	None	N
I/D	0.9991	likely_pathogenic	0.9994	pathogenic	-3.198	Highly Destabilizing	0.987	D	0.841	deleterious	None	None	None	None	N
I/E	0.997	likely_pathogenic	0.9976	pathogenic	-2.872	Highly Destabilizing	0.961	D	0.825	deleterious	None	None	None	None	N
I/F	0.8454	likely_pathogenic	0.8771	pathogenic	-1.69	Destabilizing	0.901	D	0.721	prob.delet.	N	0.514075847	None	None	N
I/G	0.9898	likely_pathogenic	0.9927	pathogenic	-3.451	Highly Destabilizing	0.961	D	0.804	deleterious	None	None	None	None	N
I/H	0.9967	likely_pathogenic	0.9977	pathogenic	-3.083	Highly Destabilizing	0.996	D	0.819	deleterious	None	None	None	None	N
I/K	0.9953	likely_pathogenic	0.9965	pathogenic	-1.995	Destabilizing	0.961	D	0.827	deleterious	None	None	None	None	N
I/L	0.3158	likely_benign	0.3652	ambiguous	-0.933	Destabilizing	0.19	N	0.414	neutral	N	0.426565931	None	None	N
I/M	0.3151	likely_benign	0.3668	ambiguous	-1.341	Destabilizing	0.901	D	0.677	prob.neutral	N	0.456145051	None	None	N
I/N	0.9862	likely_pathogenic	0.9907	pathogenic	-2.657	Highly Destabilizing	0.983	D	0.835	deleterious	N	0.485717739	None	None	N
I/P	0.9984	likely_pathogenic	0.9989	pathogenic	-1.554	Destabilizing	0.987	D	0.844	deleterious	None	None	None	None	N
I/Q	0.994	likely_pathogenic	0.9955	pathogenic	-2.307	Highly Destabilizing	0.987	D	0.839	deleterious	None	None	None	None	N
I/R	0.9911	likely_pathogenic	0.9936	pathogenic	-2.081	Highly Destabilizing	0.961	D	0.836	deleterious	None	None	None	None	N
I/S	0.9561	likely_pathogenic	0.9701	pathogenic	-3.336	Highly Destabilizing	0.901	D	0.804	deleterious	N	0.500551976	None	None	N
I/T	0.8943	likely_pathogenic	0.921	pathogenic	-2.83	Highly Destabilizing	0.722	D	0.776	deleterious	D	0.52327412	None	None	N
I/V	0.0693	likely_benign	0.0717	benign	-1.554	Destabilizing	0.001	N	0.197	neutral	N	0.329580889	None	None	N
I/W	0.9976	likely_pathogenic	0.9982	pathogenic	-1.984	Destabilizing	0.996	D	0.813	deleterious	None	None	None	None	N
I/Y	0.9861	likely_pathogenic	0.9901	pathogenic	-1.81	Destabilizing	0.961	D	0.844	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.