TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25240	75943;75944;75945	chr2:178570414;178570413;178570412	chr2:179435141;179435140;179435139
N2AB	23599	71020;71021;71022	chr2:178570414;178570413;178570412	chr2:179435141;179435140;179435139
N2A	22672	68239;68240;68241	chr2:178570414;178570413;178570412	chr2:179435141;179435140;179435139
N2B	16175	48748;48749;48750	chr2:178570414;178570413;178570412	chr2:179435141;179435140;179435139
Novex-1	16300	49123;49124;49125	chr2:178570414;178570413;178570412	chr2:179435141;179435140;179435139
Novex-2	16367	49324;49325;49326	chr2:178570414;178570413;178570412	chr2:179435141;179435140;179435139
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-71
• Domain position: 37
• Structural Position: 38
• Q(SASA): 0.1087
• 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
Y/H	rs1259012958	-3.086	1.0	D	0.816	0.867	0.785863580201	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
Y/H	rs1259012958	-3.086	1.0	D	0.816	0.867	0.785863580201	gnomAD-4.0.0	1.59268E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43295E-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
Y/A	0.9966	likely_pathogenic	0.9974	pathogenic	-3.722	Highly Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
Y/C	0.8935	likely_pathogenic	0.9168	pathogenic	-2.033	Highly Destabilizing	1.0	D	0.881	deleterious	D	0.660924104	None	None	N
Y/D	0.996	likely_pathogenic	0.9973	pathogenic	-3.914	Highly Destabilizing	1.0	D	0.916	deleterious	D	0.661327712	None	None	N
Y/E	0.9991	likely_pathogenic	0.9994	pathogenic	-3.692	Highly Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
Y/F	0.2414	likely_benign	0.273	benign	-1.543	Destabilizing	0.999	D	0.639	neutral	D	0.551081658	None	None	N
Y/G	0.9907	likely_pathogenic	0.9926	pathogenic	-4.124	Highly Destabilizing	1.0	D	0.931	deleterious	None	None	None	None	N
Y/H	0.9675	likely_pathogenic	0.9776	pathogenic	-2.838	Highly Destabilizing	1.0	D	0.816	deleterious	D	0.644904743	None	None	N
Y/I	0.9758	likely_pathogenic	0.9819	pathogenic	-2.343	Highly Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
Y/K	0.9985	likely_pathogenic	0.9992	pathogenic	-2.598	Highly Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
Y/L	0.9518	likely_pathogenic	0.9622	pathogenic	-2.343	Highly Destabilizing	0.999	D	0.741	deleterious	None	None	None	None	N
Y/M	0.985	likely_pathogenic	0.9886	pathogenic	-2.06	Highly Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
Y/N	0.9764	likely_pathogenic	0.9822	pathogenic	-3.38	Highly Destabilizing	1.0	D	0.896	deleterious	D	0.661327712	None	None	N
Y/P	0.9992	likely_pathogenic	0.9996	pathogenic	-2.824	Highly Destabilizing	1.0	D	0.942	deleterious	None	None	None	None	N
Y/Q	0.9982	likely_pathogenic	0.9988	pathogenic	-3.104	Highly Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
Y/R	0.9934	likely_pathogenic	0.996	pathogenic	-2.383	Highly Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
Y/S	0.9874	likely_pathogenic	0.9898	pathogenic	-3.681	Highly Destabilizing	1.0	D	0.907	deleterious	D	0.661327712	None	None	N
Y/T	0.9945	likely_pathogenic	0.9956	pathogenic	-3.34	Highly Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
Y/V	0.9539	likely_pathogenic	0.9625	pathogenic	-2.824	Highly Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
Y/W	0.8825	likely_pathogenic	0.9017	pathogenic	-0.713	Destabilizing	1.0	D	0.795	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.