TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14013	42262;42263;42264	chr2:178634837;178634836;178634835	chr2:179499564;179499563;179499562
N2AB	12372	37339;37340;37341	chr2:178634837;178634836;178634835	chr2:179499564;179499563;179499562
N2A	11445	34558;34559;34560	chr2:178634837;178634836;178634835	chr2:179499564;179499563;179499562
N2B	4948	15067;15068;15069	chr2:178634837;178634836;178634835	chr2:179499564;179499563;179499562
Novex-1	5073	15442;15443;15444	chr2:178634837;178634836;178634835	chr2:179499564;179499563;179499562
Novex-2	5140	15643;15644;15645	chr2:178634837;178634836;178634835	chr2:179499564;179499563;179499562
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-90
• Domain position: 49
• Structural Position: 125
• Q(SASA): 0.7263
• 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
K/T	rs1188399173	None	0.981	N	0.579	0.168	0.208000267992	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
K/T	rs1188399173	None	0.981	N	0.579	0.168	0.208000267992	gnomAD-4.0.0	5.1503E-06	None	None	None	None	N	None	1.69941E-05	3.44222E-05	None	0	0	None	0	0	0	0	2.85698E-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
K/A	0.7198	likely_pathogenic	0.6018	pathogenic	-0.17	Destabilizing	0.904	D	0.481	neutral	None	None	None	None	N
K/C	0.9055	likely_pathogenic	0.8424	pathogenic	-0.444	Destabilizing	0.999	D	0.703	prob.delet.	None	None	None	None	N
K/D	0.9327	likely_pathogenic	0.8766	pathogenic	0.273	Stabilizing	0.985	D	0.611	neutral	None	None	None	None	N
K/E	0.5528	ambiguous	0.4105	ambiguous	0.33	Stabilizing	0.877	D	0.417	neutral	N	0.434069872	None	None	N
K/F	0.9308	likely_pathogenic	0.8825	pathogenic	-0.167	Destabilizing	0.999	D	0.656	prob.neutral	None	None	None	None	N
K/G	0.8635	likely_pathogenic	0.7581	pathogenic	-0.428	Destabilizing	0.985	D	0.482	neutral	None	None	None	None	N
K/H	0.4681	ambiguous	0.403	ambiguous	-0.595	Destabilizing	0.996	D	0.571	neutral	None	None	None	None	N
K/I	0.5888	likely_pathogenic	0.4713	ambiguous	0.447	Stabilizing	0.981	D	0.709	prob.delet.	N	0.433963021	None	None	N
K/L	0.6501	likely_pathogenic	0.5221	ambiguous	0.447	Stabilizing	0.971	D	0.482	neutral	None	None	None	None	N
K/M	0.4939	ambiguous	0.3764	ambiguous	0.075	Stabilizing	0.999	D	0.575	neutral	None	None	None	None	N
K/N	0.8176	likely_pathogenic	0.7138	pathogenic	-0.013	Destabilizing	0.961	D	0.585	neutral	N	0.446914921	None	None	N
K/P	0.9953	likely_pathogenic	0.9871	pathogenic	0.27	Stabilizing	0.995	D	0.602	neutral	None	None	None	None	N
K/Q	0.2514	likely_benign	0.2049	benign	-0.092	Destabilizing	0.961	D	0.592	neutral	N	0.434096213	None	None	N
K/R	0.0965	likely_benign	0.089	benign	-0.129	Destabilizing	0.022	N	0.253	neutral	N	0.419827841	None	None	N
K/S	0.7714	likely_pathogenic	0.6686	pathogenic	-0.585	Destabilizing	0.904	D	0.543	neutral	None	None	None	None	N
K/T	0.3922	ambiguous	0.2927	benign	-0.35	Destabilizing	0.981	D	0.579	neutral	N	0.432276133	None	None	N
K/V	0.5437	ambiguous	0.441	ambiguous	0.27	Stabilizing	0.985	D	0.66	prob.neutral	None	None	None	None	N
K/W	0.9383	likely_pathogenic	0.8804	pathogenic	-0.137	Destabilizing	0.999	D	0.687	prob.delet.	None	None	None	None	N
K/Y	0.8755	likely_pathogenic	0.81	pathogenic	0.19	Stabilizing	0.995	D	0.643	neutral	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.