TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19654	59185;59186;59187	chr2:178593248;178593247;178593246	chr2:179457975;179457974;179457973
N2AB	18013	54262;54263;54264	chr2:178593248;178593247;178593246	chr2:179457975;179457974;179457973
N2A	17086	51481;51482;51483	chr2:178593248;178593247;178593246	chr2:179457975;179457974;179457973
N2B	10589	31990;31991;31992	chr2:178593248;178593247;178593246	chr2:179457975;179457974;179457973
Novex-1	10714	32365;32366;32367	chr2:178593248;178593247;178593246	chr2:179457975;179457974;179457973
Novex-2	10781	32566;32567;32568	chr2:178593248;178593247;178593246	chr2:179457975;179457974;179457973
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-30
• Domain position: 76
• Structural Position: 108
• Q(SASA): 0.0953
• 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
V/I	None	None	0.997	N	0.658	0.453	0.684766686716	gnomAD-4.0.0	3.18396E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.8664E-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
V/A	0.7137	likely_pathogenic	0.6957	pathogenic	-2.528	Highly Destabilizing	0.999	D	0.705	prob.neutral	D	0.555771124	None	None	N
V/C	0.9393	likely_pathogenic	0.9384	pathogenic	-2.217	Highly Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
V/D	0.9977	likely_pathogenic	0.9976	pathogenic	-3.505	Highly Destabilizing	1.0	D	0.905	deleterious	D	0.654325283	None	None	N
V/E	0.9946	likely_pathogenic	0.9946	pathogenic	-3.218	Highly Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
V/F	0.9492	likely_pathogenic	0.9546	pathogenic	-1.286	Destabilizing	1.0	D	0.847	deleterious	D	0.585231684	None	None	N
V/G	0.9081	likely_pathogenic	0.9049	pathogenic	-3.093	Highly Destabilizing	1.0	D	0.898	deleterious	D	0.654325283	None	None	N
V/H	0.9987	likely_pathogenic	0.9988	pathogenic	-2.856	Highly Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
V/I	0.1314	likely_benign	0.1416	benign	-0.886	Destabilizing	0.997	D	0.658	neutral	N	0.506286389	None	None	N
V/K	0.9968	likely_pathogenic	0.9969	pathogenic	-2.054	Highly Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	N
V/L	0.8095	likely_pathogenic	0.8039	pathogenic	-0.886	Destabilizing	0.997	D	0.729	prob.delet.	D	0.524723493	None	None	N
V/M	0.8818	likely_pathogenic	0.8833	pathogenic	-1.281	Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
V/N	0.9911	likely_pathogenic	0.9912	pathogenic	-2.65	Highly Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
V/P	0.9959	likely_pathogenic	0.9954	pathogenic	-1.416	Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
V/Q	0.9947	likely_pathogenic	0.9949	pathogenic	-2.342	Highly Destabilizing	1.0	D	0.892	deleterious	None	None	None	None	N
V/R	0.9926	likely_pathogenic	0.9925	pathogenic	-2.017	Highly Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
V/S	0.9414	likely_pathogenic	0.9388	pathogenic	-3.166	Highly Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
V/T	0.8882	likely_pathogenic	0.8826	pathogenic	-2.737	Highly Destabilizing	0.999	D	0.738	prob.delet.	None	None	None	None	N
V/W	0.9994	likely_pathogenic	0.9994	pathogenic	-1.873	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
V/Y	0.994	likely_pathogenic	0.9945	pathogenic	-1.623	Destabilizing	1.0	D	0.837	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.