TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31727	95404;95405;95406	chr2:178546057;178546056;178546055	chr2:179410784;179410783;179410782
N2AB	30086	90481;90482;90483	chr2:178546057;178546056;178546055	chr2:179410784;179410783;179410782
N2A	29159	87700;87701;87702	chr2:178546057;178546056;178546055	chr2:179410784;179410783;179410782
N2B	22662	68209;68210;68211	chr2:178546057;178546056;178546055	chr2:179410784;179410783;179410782
Novex-1	22787	68584;68585;68586	chr2:178546057;178546056;178546055	chr2:179410784;179410783;179410782
Novex-2	22854	68785;68786;68787	chr2:178546057;178546056;178546055	chr2:179410784;179410783;179410782
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTA
• RefSeq wild type template codon: AAT
• Domain: Fn3-119
• Domain position: 20
• Structural Position: 22
• Q(SASA): 0.114
• 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
L/S	None	None	0.994	D	0.795	0.685	0.871487081793	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	1.94099E-04	0	None	0	0	1.3125E-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
L/A	0.8145	likely_pathogenic	0.8658	pathogenic	-2.367	Highly Destabilizing	0.97	D	0.719	prob.delet.	None	None	None	None	N
L/C	0.8391	likely_pathogenic	0.8817	pathogenic	-1.646	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	N
L/D	0.9995	likely_pathogenic	0.9996	pathogenic	-2.803	Highly Destabilizing	0.999	D	0.887	deleterious	None	None	None	None	N
L/E	0.9952	likely_pathogenic	0.9965	pathogenic	-2.47	Highly Destabilizing	0.999	D	0.863	deleterious	None	None	None	None	N
L/F	0.5936	likely_pathogenic	0.6606	pathogenic	-1.394	Destabilizing	0.989	D	0.657	neutral	D	0.533987933	None	None	N
L/G	0.984	likely_pathogenic	0.9903	pathogenic	-2.999	Highly Destabilizing	0.996	D	0.852	deleterious	None	None	None	None	N
L/H	0.9908	likely_pathogenic	0.9937	pathogenic	-2.833	Highly Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
L/I	0.098	likely_benign	0.1064	benign	-0.481	Destabilizing	0.835	D	0.605	neutral	D	0.528837442	None	None	N
L/K	0.9938	likely_pathogenic	0.9946	pathogenic	-1.64	Destabilizing	0.996	D	0.786	deleterious	None	None	None	None	N
L/M	0.242	likely_benign	0.2852	benign	-0.724	Destabilizing	0.746	D	0.368	neutral	None	None	None	None	N
L/N	0.9966	likely_pathogenic	0.9976	pathogenic	-2.318	Highly Destabilizing	0.999	D	0.891	deleterious	None	None	None	None	N
L/P	0.9926	likely_pathogenic	0.995	pathogenic	-1.098	Destabilizing	0.999	D	0.885	deleterious	None	None	None	None	N
L/Q	0.9844	likely_pathogenic	0.9886	pathogenic	-1.918	Destabilizing	0.996	D	0.847	deleterious	None	None	None	None	N
L/R	0.9857	likely_pathogenic	0.9884	pathogenic	-1.866	Destabilizing	0.996	D	0.846	deleterious	None	None	None	None	N
L/S	0.9842	likely_pathogenic	0.9905	pathogenic	-2.937	Highly Destabilizing	0.994	D	0.795	deleterious	D	0.556499961	None	None	N
L/T	0.8944	likely_pathogenic	0.9261	pathogenic	-2.424	Highly Destabilizing	0.97	D	0.728	prob.delet.	None	None	None	None	N
L/V	0.0837	likely_benign	0.0944	benign	-1.098	Destabilizing	0.122	N	0.289	neutral	N	0.510979613	None	None	N
L/W	0.9716	likely_pathogenic	0.9803	pathogenic	-1.791	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
L/Y	0.9711	likely_pathogenic	0.9769	pathogenic	-1.503	Destabilizing	0.999	D	0.737	prob.delet.	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.